http://www.labspaces.net/117757/Rese...nson_s_disease

Researchers reveal role of protein mutation in Parkinson's diseaseTuesday, February 21, 2012



This is Fred Regnier. Credit: Purdue News Service Purdue University researchers revealed how a mutation in a protein shuts down a protective function needed to prevent the death of neurons in Parkinson's disease, possibly opening the door to new drug strategies to treat the disorder.

Fred Regnier, the J.H. Law Distinguished Professor of Chemistry, and Jean-Christophe Rochet, an associate professor of medicinal chemistry and molecular pharmacology, led the team that discovered how the protein DJ-1, which plays a significant role in protecting neurons from damage, is shut down by a subtle mutation.

A substitution in one link of the chain of amino acids that makes up the protein renders it unable to be activated to protect neurons from the build up of protein "aggregates," or "clumps," that lead to cell death in those with Parkinson's disease.

"The saying that you are only as strong as your weakest link appears to hold true in the case of the chain of amino acids that make up a protein," Regnier said. "The magnitude of the effect of this subtle change is surprising. It can make the difference between having a disease and being healthy."

According to the Parkinson's Disease Foundation, an estimated 7 million to 10 million people worldwide are living with the disease, which is a neurodegenerative disorder that causes muscular rigidity, slowness of movement, poor balance and tremors. The death of neurons in a region of the brain called the substantia nigra cause the symptoms.

The findings of the Purdue-led study could potentially lead to new Parkinson's treatments, Rochet said.

"The current methods of treatment are to add back what the lost cells used to produce, similar to hormone replacement therapies," he said. "Understanding this error in a key protein could help researchers find a way to prevent cell death in the first place. Perhaps a compound could be found that could correct the problem and resurrect the protective function of the protein. Of course interventions would be needed in many places to treat the disease, but this could be one of several places to target for a potential treatment."

When functioning properly, DJ-1 appears to serve as a "chaperone" protein for the neural protein alpha-synuclein, escorting and protecting it as it performs its biological task. Without the help of DJ-1, alpha-synuclein can unfold and expose sticky surfaces that cause it to clump together with other proteins. These clumps are a component of the "Lewy bodies" and other protein deposits that build up in the neurons of Parkinson's disease patients and cause the cells to die, he said.

About 10 years ago it was discovered that people with familial, early-onset Parkinson's disease had a mutation in the gene that encodes DJ-1 that leads to a mutant form of the protein through a substitution in one of the protein's amino acids.

The Purdue-led team developed a new quantitative mass spectrometry approach to evaluate and compare the mutant and normal protein. They discovered that the substitution prevents DJ-1 from undergoing an important chemical reaction in which oxygen is added to a specific site on the protein. This addition of oxygen takes the protein into a two-oxygen form that facilitates its chaperone function.

It had been thought that the amino acid substitution led to an unfolding of the protein, but the team found that it instead slightly alters the structure of the active site pocket, preventing the addition of oxygen at that site.

In addition the team found that the attachment of too much oxygen or an oxygen atom linked at the wrong location also disabled the protein's protective abilities, Rochet said.

"The interaction of this protein with oxygen needs to be very precise," Rochet said. "We need just enough oxygen added at just the right site to activate the protective ability of the protein, but too much oxygen or oxygen added at the wrong location causes real problems."

Because the precise oxidation of the protein may play a significant role in preventing the development of Parkinson's disease, evaluation of the levels of oxidized DJ-1, non-oxidized DJ-1 and over-oxidized DJ-1 could be the starting point of a new diagnosis method, Regnier said.

"Mass spectrometers could be used to find specific forms of DJ-1 and changes in the levels of these different forms could lead to a diagnosis of the disease," he said. "If we could find that a certain form or ratio appears early in disease development, we might be able to catch it and treat it earlier."

The team's findings are detailed in a paper in the February issue of the journal Molecular and Cellular Proteomics. In addition to Regnier and Rochet, paper co-authors include postdoctoral research associate Ashraf G. Madian and graduate student Naomi Diaz-Maldonado of the Purdue Department of Chemistry; graduate students Jagadish Hindupur and Vartika R. Mishra and former graduate student John D. Hulleman of the Purdue Department of Medicinal Chemistry and Molecular Pharmacology; and Emmanuel Guigard and Cyril M. Kay from the Department of Biochemistry at the University of Alberta, Canada.

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"Understanding this error in a key protein could help researchers find a way to prevent cell death in the first place. Perhaps a compound could be found that could correct the problem and resurrect the protective function of the protein."

This is what I want to hear. Keep going researchers, full speed ahead, per favore!

PQQ protects against the self-oxidation of the DJ-1 gene. Pyrroloquinoline quinone (PQQ) is available as a supplement.

thanks for that - are there any recommended suppliers ?

It's expensive in the UK

From what I read, it looks like the DJ-1 mutation is particular to those carrying the PARK 1-10 genes.

I am wondering if taking PQQ is appropriate for those whose PD is caused by other genetic mutations. In my case, the mutation involves GBA.

http://forums.steroid.com/archive/in.../t-486298.html

I suggest the Life Extension Foundation

www.lef.org

I just bought some at my local health food market by LifeExtension.
They cost $17.99 for 30 capsules of 10 mg. about $.60/day.

This is what Wiki has to say:

Pyrroloquinoline quinone
From Wikipedia, the free encyclopedia

Pyrroloquinoline quinone (PQQ) was discovered by J.G. Hauge as the third redox cofactor after nicotinamide and flavin in bacteria (although they hypothesised that it was naphthoquinone).[1] Anthony and Zatman also found the unknown redox cofactor in alcohol dehydrogenase and named it methoxatin.[2] In 1979, Salisbury and colleagues[3] as well as Duine and colleagues[4] extracted this prosthetic group from methanol dehydrogenase of methylotrophs and identified its molecular structure. Adachi and colleagues identified that PQQ was also found in Acetobacter.[5]

These enzymes containing PQQ are called quinoproteins. Glucose dehydrogenase, one of the quinoproteins, is used as a glucose sensor. Subsequently, PQQ was found to stimulate growth in bacteria.[6] In addition, antioxidant and neuro-protective effects were also found.[7]

In 1989, Rucker and colleagues reported that mice deprived of PQQ showed various abnormalities, and it was suggested that PQQ may also have an important nutritional role in other mammals.[8] In 2003, it was reported that aminoadipate semialdehyde dehydrogenase (AASDH) might also use PQQ as a cofactor, suggesting a possibility that PQQ is a vitamin in mammals.[9] Rucker and colleagues concluded that insufficient information is available so far to state that PQQ is a vitamin for mammals, although PQQ may be an important biological factor.[10]

It was recently shown that PQQ may stimulate growth of plants (cucumbers and tomatoes) in hydroponic culture and may be the causative factor in plant growth stimulation by a strain of Pseudomonas fluorescens bacterium.[11]

PQQ as a prosthetic group on glucose dehydrogenase has been utilized at the anode in an enzyme based fuel cell. [12]

Supplementation benefits

PQQ is taken as a dietary supplement to support mitochondrial health and cellular energy production, and to protect the body from oxidative stress. Most notably, PQQ stimulates the spontaneous growth of new mitochondria in aging cells, and activates genes that govern mitochondrial reproduction, protection, and repair.

Antioxidant capacity and role in mitochondrial health

Mitochondria are the primary engines of almost all bioenergy production in the human body and are among the most vulnerable physiological structures to destruction from oxidative damage. Scientists now recognize mitochondrial dysfunction as a key biomarker of aging.[13] [14][15][16][17][18]Relative to cellular DNA, mitochondrial DNA possesses few defenses against free radical damage, and is dependent upon antioxidants for protection. [19][20]PQQ’s powerful free radical–scavenging capacity provides the mitochondria with superior antioxidant protection due to its high molecular stability and the role it plays in energy transfer directly within the mitochondria. Unlike other antioxidants, the exceptional molecular stability of PQQ allows it to carry out thousands of electron transfers without undergoing molecular breakdown [21]

PQQ is especially effective in neutralizing superoxide and hydroxyl radicals,[22][23] two prominent causes of mitochondrial dysfunction.

According to a University of California at Davis study, “PQQ is 30 to 5,000 times more efficient in sustaining redox cycling (mitochondrial energy production) . . . than other common [antioxidant compounds], e.g. Ascorbic Acid (Vitamin C).”[24]

[edit] Mitochondrial biogenesis

In 2010, researchers at the University of California at Davis released a peer-reviewed publication showing that PQQ’s critical role in growth and development stems from its unique ability to activate cell signaling pathways directly involved in cellular energy metabolism, development, and function.

Most significantly, the study demonstrated that PQQ not only protects mitochondria from oxidative stress—it promotes the spontaneous generation of new mitochondria within aging cells, a process known as mitochondrial biogenesis.[25] The implications of this revelation for human health and longevity are significant because the only other known methods proven to stimulate mitochondiral biogenesis in aging humans are intense aerobic exercise,[26] strict caloric restriction,[27] and certain medications such as thiazolidinediones[28] and the diabetes drug metformin.[29]

[edit] Activation of signaling molecules

The team of researchers at the University of California analyzed PQQ’s influence over cell signaling pathways involved in the generation of new mitochondria and found that there are three signaling molecules activated by PQQ that cause cells to undergo spontaneous mitochondrial biogenesis:[25]

PQQ activates expression of PCG-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha), a “master regulator” that mobilizes cells’ response to various external triggers. It directly stimulates genes that enhance mitochondrial and cellular respiration, growth, and reproduction. Its capacity to upregulate cellular metabolism at the genetic level favorably affects blood pressure, cholesterol and triglyceride breakdown, and the onset of obesity.[30]

PQQ triggers the CREB signaling protein (cAMP-response element-binding protein), which plays a pivotal role in embryonic development and growth. It also beneficially interacts with histones, molecular compounds shown to protect and repair cellular DNA.[31] CREB also stimulates the growth of new mitochondria.

PQQ regulates a recently discovered cell signaling protein called DJ-1. As with PCG-1α and CREB, DJ-1 is intrinsically involved in cell function and survival, has been shown to prevent cell death by combating intensive antioxidant stress,[32][33]and is of particular importance to brain health and function. DJ-1 damage and mutation have been conclusively linked to the onset of Parkinson’s disease and other neurological disorders.

[edit] Neuroprotection

PQQ is a potent neuroprotective nutrient that has been shown to protect memory and cognition in both aging animals and humans.[34][35] It has been shown to reverse cognitive impairment caused by chronic oxidative stress in pre-clinical models and improve performance on memory tests.[36] PQQ supplementation stimulates the production and release of nerve growth factor in cells that support neurons in the brain,[37] a possible explanation for the marked improvement of memory function it produces in aging humans and rats.

PQQ has also been shown to safeguard against the self-oxidation of the DJ-1 gene, an early step in the onset of Parkinson’s disease.[38]

PQQ protects brain cells against oxidative damage following ischemia-reperfusion injury—the inflammation and oxidative damage that result from the sudden return of blood and nutrients to tissues deprived of them by stroke.[39] Reactive nitrogen species (RNS) arise spontaneously following stroke and spinal cord injuries and impose severe stresses on damaged neurons, producing a significant proportion of subsequent long-term neurological damage.[40] PQQ suppresses RNS in experimentally induced strokes,[41] and provides additional protection following spinal cord injury by blocking inducible nitric oxide synthase (iNOS), a major source of RNS.[42]

In animal models, administration of PQQ immediately prior to induction of stroke significantly reduces the size of the damaged brain area.[43] These observations have been extended in vivo by showing that PQQ protects against the likelihood of severe stroke in an experimental animal model for stroke and brain hypoxia. [39]

PQQ interacts beneficially with the brain’s neurotransmitter systems. It protects neurons by modifying the N-methyl-D-aspartate (NMDA) receptor.[44][45] and inhibiting excitotoxicity—the damaging consequence of long-term overstimulation of neurons that is associated with many neurodegenerative diseases and seizures. [46][47][48][49]

PQQ also protects the brain against neurotoxicity induced by other powerful toxins, including mercury[50](a suspected factor in the development of Alzheimer’s disease[51]) and oxidopamine[22] (a potent neurotoxin used by scientists to induce Parkinsonism in laboratory animals by destroying dopaminergic and noradrenergic neurons.[52])

PQQ prevents aggregation of alpha-synuclein, a protein associated with Parkinson’s disease.[53] PQQ also protects nerve cells from the oxidizing ravages of the amyloid-beta protein linked with Alzheimer’s disease,[54] and works preventatively to block new amyloid beta molecular structures from forming before they can cause any damage.[55]
[edit] Cognition

PQQ has been shown to promote memory, attention, and cognition in animals[34] and humans.

In a double-blind, placebo-controlled clinical trial conducted in Japan in 2007, supplementation with 20 mg per day of PQQ resulted in improvements on tests of higher cognitive function in a group of 71 middle-aged and elderly people aged between 40-70, who outperformed the placebo group by more than twofold in their standardized memory tests.[35]

Interestingly, the results of the study also suggest a synergistic relationship between PQQ and the nutrient coenzyme Q10 (CoQ10), which further amplified performance on standardized memory tests when subjects also took 300 mg per day of CoQ10. No adverse effects were linked to the supplementation, and the results demonstrated that PQQ, especially when combined with CoQ10, can be used to improve mental status and quality of life in older patients, and help slow or prevent age-related cognitive decline in middle-age patients.
[edit] Cardioprotection

Damage from a heart attack, like a stroke, is inflicted via ischemia-reperfusion injury. Supplemental PQQ reduces the size of damaged areas in animal models of acute heart attack (myocardial infarction). Significantly, this occurs whether the supplement is given before or after the ischemic event itself, suggesting that supplementation within the first hours of medical response may offer profound benefits to heart attack victims.[56]

Researches at the University of California at San Francisco investigated this potential, comparing PQQ with the beta blocker metoprolol—a standard post-MI clinical treatment. Independently, both treatments reduced the size of the damaged areas’ and protected against heart muscle dysfunction. When given together, the left ventricle’s pumping pressure was enhanced. The combination of PQQ with metoprolol also increased mitochondrial energy-producing functions—but the effect was modest compared with PQQ alone. Only PQQ favorably reduced lipid peroxidation. These results led the researches to conclude that “PQQ is superior to metoprolol in protecting mitochondria from ischemia/reperfusion oxidative damage.” [57]]

Subsequent research has also demonstrated that PQQ helps heart muscle cells resist acute oxidative stress by preserving and enhancing mitochondrial function. [58]
[edit] Supplement dosage

Despite its classification as an essential nutrient,[41] no recommended daily intake of PQQ has been established.

Animal studies have demonstrated PQQ's support of healthy mitochondrial function with human equivalent dose (H.E.D.) as low as 1.44 milligrams per day,[59] the majority of actual human studies have used higher doses of 10-20mg or more. Consequently, nearly all PQQ supplements sold in the United States range from 10–20 mg.[60][unreliable source?]
[edit] References

^ Hauge JG (1964). "Glucose dehydrogenase of bacterium anitratum: an enzyme with a novel prosthetic group". J Biol Chem 239: 3630–9. PMID 14257587.
^ Anthony C, Zatman LJ (1967). "The microbial oxidation of methanol. The prosthetic group of the alcohol dehydrogenase of Pseudomonas sp. M27: a new oxidoreductase prosthetic group". Biochem J 104 (3): 960–9. PMC 1271238. PMID 6049934.
^ Salisbury SA, Forrest HS, Cruse WB, Kennard O (1979). "A novel coenzyme from bacterial primary alcohol dehydrogenases". Nature 280 (5725): 843–4. doi:10.1038/280843a0. PMID 471057.
^ Westerling J, Frank J, Duine JA (1979). "The prosthetic group of methanol dehydrogenase from Hyphomicrobium X: electron spin resonance evidence for a quinone structure". Biochem Biophys Res Commun 87 (3): 719–24. doi:10.1016/0006-291X(79)92018-7. PMID 222269.
^ Ameyama M, Matsushita K, Ohno Y, Shinagawa E, Adachi O (1981). "Existence of a novel prosthetic group, PQQ, in membrane-bound, electron transport chain-linked, primary dehydrogenases of oxidative bacteria". FEBS Lett 130 (2): 179–83. doi:10.1016/0014-5793(81)81114-3. PMID 6793395.
^ Ameyama M, Matsushita K, Shinagawa E, Hayashi M, Adachi O (1988). "Pyrroloquinoline quinone: excretion by methylotrophs and growth stimulation for microorganisms". Biofactors 1 (1): 51–3. PMID 2855583.
^ Rucker R, Chowanadisai W, Nakano M. (2009). "Potential physiological importance of pyrroloquinoline quinone". Altern Med Rev. 14 (3): 179–83.
^ Killgore J, Smidt C, Duich L, Romero-Chapman N, Tinker D, Reiser K, Melko M, Hyde D, Rucker RB (1989). "Nutritional importance of pyrroloquinoline quinone". Science 245 (4920): 850–2. doi:10.1126/science.2549636. PMID 2549636.
^ Kasahara T, Kato T (2003). "Nutritional biochemistry: A new redox-cofactor vitamin for mammals". Nature 422 (6934): 832. doi:10.1038/422832a. PMID 12712191.
^ Rucker R, Storms D, Sheets A, Tchaparian E, Fascetti A (2005). "Biochemistry: is pyrroloquinoline quinone a vitamin?". Nature 433 (7025): E10–1; discussion E11–2. doi:10.1038/nature03323. PMID 15689994.
^ Choi, O., Kim, J., Kim, J.-G., Jeong, Y., Moon, J. S., Park, C. S., Hwang, I. (2008). "PLANTS INTERACTING WITH OTHER ORGANISMS Pyrroloquinoline Quinone Is a Plant Growth Promotion Factor Produced by Pseudomonas fluorescens B16". Plant Physiology 146 (2): 657–668. doi:10.1104/pp.107.112748. PMC 2245851. PMID 18055583.
^ Noriko Yuhashia, Masamitsu Tomiyamab, Junko Okudaa, Satoshi Igarashia, Kazunori Ikebukuroa and Koji Sodea, (2005). "Development of a novel glucose enzyme fuel cell system employing protein engineered PQQ glucose dehydrogenase". Biosensors and Bioelectronics 20 (10): 2145–2150. doi:10.1016/j.bios.2004.08.017. PMID 15741089.
^ Bliznakov, EG (Dec 1999). "Aging, mitochondria, and coenzyme Q(10): the neglected relationship". Biochimie. 81 (81(12)): 1131–2. PMID 10917692.
^ Linnane, AW; Marzuki, S; Ozawa, T; Tanaka, M (1989). "Mitochondrial DNA mutations as an important contributor to ageing and degenerative diseases". Lancet 1 (8639): 642–5. doi:10.1016/S0140-6736(89)92145-4. PMID 2564461. edit
^ Lanza, IR; Nair, KS (2010 Sep). "Mitochondrial metabolic function assessed in vivo and in vitro". Current Opinion in Clinical Nutrition and Metabolic Care 13 (5): 511–7. doi:10.1097/MCO.0b013e32833cc93d. PMID 20616711. edit
^ Mota, MP; Peixoto, FM; Soares, JF; Figueiredo, PA; Leitão, JC; Gaivão, I; Duarte, JA (2010 Sep). "Influence of aerobic fitness on age-related lymphocyte DNA damage in humans: relationship with mitochondria respiratory chain and hydrogen peroxide production". Age (Dordrecht, Netherlands) 32 (3): 337–46. doi:10.1007/s11357-010-9138-8. PMC 2926856. PMID 20640548. edit
^ Tranah, GJ (2011 Apr). "Mitochondrial-nuclear epistasis: Implications for human aging and longevity". Ageing Research Reviews 10 (2): 238–52. doi:10.1016/j.arr.2010.06.003. PMC 2995012. PMID 20601194. edit
^ Cho, DH; Nakamura, T; Lipton, SA (2010 Oct). "Mitochondrial dynamics in cell death and neurodegeneration". Cellular and Molecular Life Sciences 67 (20): 3435–47. doi:10.1007/s00018-010-0435-2. PMID 20577776. edit
^ Richter, C (1995). "Oxidative damage to mitochondrial DNA and its relationship to ageing". The international journal of biochemistry & cell biology 27 (7): 647–53. PMID 7648420. edit
^ Miquel, J (1992). "An update on the mitochondrial-DNA mutation hypothesis of cell aging". Mutation research 275 (3-6): 209–16. PMID 1383762. edit
^ Paz, MA; Martin, P; Flückiger, R; Mah, J; Gallop, PM (1996 Jul). "The catalysis of redox cycling by pyrroloquinoline quinone (PQQ), PQQ derivatives, and isomers and the specificity of inhibitors". Analytical Biochemistry 238 (2): 145–9. doi:10.1006/abio.1996.0267. PMID 8660603. edit
^ a b Hara, H; Hiramatsu, H; Adachi, T (2007 Mar). "Pyrroloquinoline quinone is a potent neuroprotective nutrient against 6-hydroxydopamine-induced neurotoxicity". Neurochemical Research 32 (3): 489–95. doi:10.1007/s11064-006-9257-x. PMID 17268846. edit
^ Urakami, T; Yoshida, C; Akaike, T; Maeda, H; Nishigori, H; Niki, E (1997). "Synthesis of monoesters of pyrroloquinoline quinone and imidazopyrroloquinoline, and radical scavenging activities using electron spin resonance in vitro and pharmacological activity in vivo". Journal of nutritional science and vitaminology 43 (1): 19–33. PMID 9151238. edit
^ Stites, TE; Mitchell, AE; Rucker, RB (2000). "Physiological importance of quinoenzymes and the O-quinone family of cofactors". The Journal of nutrition 130 (4): 719–27. PMID 10736320. edit
^ a b Chowanadisai, W; Bauerly, KA; Tchaparian, E; Wong, A; Cortopassi, GA; Rucker, RB (2010 Jan). "Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1alpha expression". Journal of Biological Chemistry 285 (1): 142–52. doi:10.1074/jbc.M109.030130. PMC 2804159. PMID 19861415. edit
^ Lanza, IR; Sreekumaran Nair, K (2010 Aug). "Regulation of skeletal muscle mitochondrial function: genes to proteins". Acta Physiologica 199 (4): 529–47. doi:10.1111/j.1748-1716.2010.02124.x. PMID 20345409. edit
^ Spindler, SR (2010 Jul). "Caloric restriction: from soup to nuts". Ageing Research Reviews 9 (3): 324–53. doi:10.1016/j.arr.2009.10.003. PMID 19853062. edit
^ Fujisawa, K.; Nishikawa, T.; Kukidome, D.; Imoto, K.; Yamashiro, T.; Motoshima, H.; Matsumura, T.; Araki, E. (2009). "TZDs reduce mitochondrial ROS production and enhance mitochondrial biogenesis". Biochemical and Biophysical Research Communications 379 (1): 43–48. doi:10.1016/j.bbrc.2008.11.141. PMID 19084501. edit
^ Suwa, M; Egashira, T; Nakano, H; Sasaki, H; Kumagai, S (2006 Dec). "Metformin increases the PGC-1alpha protein and oxidative enzyme activities possibly via AMPK phosphorylation in skeletal muscle in vivo". Journal of Applied Physiology 101 (6): 1685–92. doi:10.1152/japplphysiol.00255.2006. PMID 16902066. edit
^ "Entrez Gene: PPARGC1A peroxisome proliferator-activated receptor gamma, coactivator 1 alpha [ Homo sapiens GeneID: 10891"].
^ "Entrez Gene: CREBBP CREB binding protein [ Homo sapiens GeneID: 1387"].
^ Mitsumoto, A; Nakagawa, Y (2001). "DJ-1 is an indicator for endogenous reactive oxygen species elicited by endotoxin". Free radical research 35 (6): 885–93. PMID 11811539. edit
^ Taira, T; Saito, Y; Niki, T; Iguchi-Ariga, SMM; Takahashi, K; Ariga, H (2004 Feb). "DJ-1 has a role in antioxidative stress to prevent cell death". EMBO Reports 5 (2): 213–8. doi:10.1038/sj.embor.7400074. PMC 1298985. PMID 14749723. edit
^ a b Takatsu, H; Owada, K; Abe, K; Nakano, M; Urano, S (2009). "Effect of vitamin E on learning and memory deficit in aged rats". Journal of nutritional science and vitaminology 55 (5): 389–93. PMID 19926923. edit
^ a b "Effect of pyrroloquinoline quinone (PQQ) on mental status of middle-aged and elderly persons". Food Style 21 13 (7): 50–52. 2009.
^ Ohwada, K; Takeda, H; Yamazaki, M; Isogai, H; Nakano, M; Shimomura, M; Fukui, K; Urano, S (2008 Jan). "Pyrroloquinoline quinone (PQQ) prevents cognitive deficit caused by oxidative stress in rats". Journal of Clinical Biochemistry and Nutrition 42: 29–34. doi:10.3164/jcbn.2008005. PMC 2212345. PMID 18231627. edit
^ Murase, K; Hattori, A; Kohno, M; Hayashi, K (1993). "Stimulation of nerve growth factor synthesis/secretion in mouse astroglial cells by coenzymes". Biochemistry and molecular biology international 30 (4): 615–21. PMID 8401318. edit
^ Nunome, K; Miyazaki, S; Nakano, M; Iguchi-Ariga, S; Ariga, H (2008). "Pyrroloquinoline quinone prevents oxidative stress-induced neuronal death probably through changes in oxidative status of DJ-1". Biological & pharmaceutical bulletin 31 (7): 1321–6. PMID 18591768. edit
^ a b Jensen, FE; Gardner, GJ; Williams, AP; Gallop, PM; Aizenman, E; Rosenberg, PA (1994). "The putative essential nutrient pyrroloquinoline quinone is neuroprotective in a rodent model of hypoxic/ischemic brain injury". Neuroscience 62 (2): 399–406. doi:10.1016/0306-4522(94)90375-1. PMID 7830887. edit
^ Ono, K; Suzuki, H; Sawada, M (2010 Apr 5). "Delayed neural damage is induced by iNOS-expressing microglia in a brain injury model". Neuroscience Letters 473 (2): 146–150. doi:10.1016/j.neulet.2010.02.041. PMID 20178828. edit
^ a b Zhang, Y; Rosenberg, PA (2002). "The essential nutrient pyrroloquinoline quinone may act as a neuroprotectant by suppressing peroxynitrite formation". The European journal of neuroscience 16 (6): 1015–24. PMID 12383230. edit
^ Hirakawa, A; Shimizu, K; Fukumitsu, H; Furukawa, S (2009 Jan 9). "Pyrroloquinoline quinone attenuates iNOS gene expression in the injured spinal cord". Biochemical and Biophysical Research Communications 378 (2): 308–12. doi:10.1016/j.bbrc.2008.11.045. PMID 19026989. edit
^ Zhang, Y; Feustel, P; Kimelberg, H (2006 Jun 13). "Neuroprotection by pyrroloquinoline quinone (PQQ) in reversible middle cerebral artery occlusion in the adult rat". Brain Research 1094 (1): 200–6. doi:10.1016/j.brainres.2006.03.111. PMID 16709402. edit
^ Aizenman, E; Hartnett, KA; Zhong, C; Gallop, PM; Rosenberg, PA (1992). "Interaction of the putative essential nutrient pyrroloquinoline quinone with the N-methyl-D-aspartate receptor redox modulatory site". Journal of Neuroscience 12 (6): 2362–9. PMID 1318959. edit
^ Aizenman, E; Jensen, FE; Gallop, PM; Rosenberg, PA; Tang, LH (1994). "Further evidence that pyrroloquinoline quinone interacts with the N-methyl-D-aspartate receptor redox site in rat cortical neurons in vitro". Neuroscience letters 168 (1-2): 189–92. doi:10.1016/0304-3940(94)90447-2. PMID 7518062. edit
^ Scanlon, JM; Aizenman, E; Reynolds, IJ (1997). "Effects of pyrroloquinoline quinone on glutamate-induced production of reactive oxygen species in neurons". European journal of pharmacology 326 (1): 67–74. doi:10.1016/S0014-2999(97)00137-4. PMID 9178657. edit
^ Hossain, MA (2005 Sep). "Molecular mediators of hypoxic-ischemic injury and implications for epilepsy in the developing brain". Epilepsy & Behavior 7 (2): 204–213. doi:10.1016/j.yebeh.2005.05.015. PMID 16054439. edit
^ Dong, XX; Wang, Y; Qin, ZH (2009 Apr). "Molecular mechanisms of excitotoxicity and their relevance to pathogenesis of neurodegenerative diseases". Acta Pharmacologica Sinica 30 (4): 379–87. doi:10.1038/aps.2009.24. PMID 19343058. edit
^ Foran, E; Trotti, D (2009 Jul). "Glutamate transporters and the excitotoxic path to motor neuron degeneration in amyotrophic lateral sclerosis". Antioxidants & Redox Signaling 11 (7): 1587–602. doi:10.1089/ars.2009.2444. PMID 19413484. edit
^ Zhang, P; Xu, Y; Sun, J; Li, X; Wang, L; Jin, L (2009 Mar). "Protection of pyrroloquinoline quinone against methylmercury-induced neurotoxicity via reducing oxidative stress". Free Radical Research 43 (3): 224–33. doi:10.1080/10715760802677348. PMID 19191107. edit
^ Mutter J, C. A. (2010). "Does inorganic mercury play a role in Alzheimer's disease? A systematic review and an integrated molecular mechanism". Journal of Alzheimer's Disease 22 (2): 357–374. doi:10.3233/JAD-2010-100705. PMID 20847438. edit
^ Breese, GR; Knapp, DJ; Criswell, HE; Moy, SS; Papadeas, ST; Blake, BL (2005 Feb). "The neonate-6-hydroxydopamine-lesioned rat: a model for clinical neuroscience and neurobiological principles". Brain Research Reviews 48 (1): 57–73. doi:10.1016/j.brainresrev.2004.08.004. PMID 15708628. edit
^ Kobayashi, M; Kim, J; Kobayashi, N; Han, S; Nakamura, C; Ikebukuro, K; Sode, K (2006 Oct 27). "Pyrroloquinoline quinone (PQQ) prevents fibril formation of alpha-synuclein". Biochemical and Biophysical Research Communications 349 (3): 1139–44. doi:10.1016/j.bbrc.2006.08.144. PMID 16962995. edit
^ Zhang JJ; Zhang RF; Meng XK (2009 Oct 30). "Protective effect of pyrroloquinoline quinone against Abeta-induced neurotoxicity in human neuroblastoma SH-SY5Y cells". Neuroscience Letters 464 (3): 165–9. doi:10.1016/j.neulet.2009.08.037. PMID 19699263. edit
^ Kim, J; Kobayashi, M; Fukuda, M; Ogasawara, D; Kobayashi, N; Han, S; Nakamura, C; Inada, M et al (2010). "Pyrroloquinoline quinone inhibits the fibrillation of amyloid proteins". Prion 4 (1): 26–31. PMC 2850417. PMID 20083898. edit
^ Zhu BQ, Zhou HZ, Teerlink JR, Karliner JS (2004 Nov). "Pyrroloquinoline quinone (PQQ) decreases myocardial infarct size and improves cardiac function in rat models of ischemia and ischemia/reperfusion". Cardiovascular Drugs and Therapy 18 (6): 421-31. doi:10.1007/s10557-004-6219-x. PMID 15770429. edit
^ Zhu BQ; Simonis U; Cecchini G; Zhou HZ; Li L; Teerlink JR; Karliner JS (2006 Jun). "Comparison of pyrroloquinoline quinone and/or metoprolol on myocardial infarct size and mitochondrial damage in a rat model of ischemia/reperfusion injury". Journal of Cardiovascular Pharmacology and Therapeutics 11 (2): 119–28. doi:10.1177/1074248406288757. PMID 16891289. edit
^ Tao, R; Karliner, J; Simonis, U; Zheng, J; Zhang, J; Honbo, N; Alano, C (2007). "Pyrroloquinoline quinone preserves mitochondrial function and prevents oxidative injury in adult rat cardiac myocytes". Biochemical and Biophysical Research Communications 363 (2): 257–62. doi:10.1016/j.bbrc.2007.08.041. PMC 2844438. PMID 17880922. edit
^ Stites, T; Storms, D; Bauerly, K; Mah, J; Harris, C; Fascetti, A; Rogers, Q; Tchaparian, E et al (2006). "Pyrroloquinoline quinone modulates mitochondrial quantity and function in mice". The Journal of nutrition 136 (2): 390–6. PMID 16424117. edit
^ "PQQ Dosage; What size pyrroloquinoline quinone pills should I take?".

LEF.org has a nice summary about PQQ: http://www.lef.org/magazine/mag2011/...hondria_01.htm

Excerpt: "PQQ stimulates natural production of nerve growth factor (NGF)4,5 which triggers growth and branching of nerve cells.33 Nerve growth factor is vital in repairing damage caused by a stroke, by ischemia (loss of blood flow), or by an injury. In other words, PQQ shows promise in stimulating brain and nerve tissue to heal itself.34"

Isn't this what Cogane is supposed to do? I wonder how they compare?