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-   -   Hypothesis for brain failure --proteinopathy and neuronal senescence (https://www.neurotalk.org/parkinson-s-disease/105463-hypothesis-brain-failure-proteinopathy-neuronal-senescence.html)

olsen 10-12-2009 09:10 PM

Hypothesis for brain failure --proteinopathy and neuronal senescence
 
Proteinopathy-induced neuronal senescence: a hypothesis for brain failure in Alzheimer's and other neurodegenerative diseases
Todd E Golde, Victor M Miller

Alzheimer's Research & Therapy 2009, 1:5 (12 October 2009)
http://alzres.com/content/1/2/5/abstract

Alzheimer's disease (AD) and a host of other neurodegenerative central nervous system (CNS) proteinopathies are characterized by the accumulation of misfolded protein aggregates. Simplistically, these aggregates can be divided into smaller, soluble, oligomeric and larger, less-soluble or insoluble, fibrillar forms.

Perhaps the major ongoing debate in the neurodegenerative disease field is whether the smaller oligomeric or larger fibrillar aggregates are the primary neurotoxin. Herein, we propose an integrative hypothesis that provides new insights into how a variety of misfolded protein aggregates can result in neurodegeneration.

Results: We introduce the concept that a wide range of highly stable misfolded protein aggregates in AD and other neurodegenerative proteinopathies are recognized as non-self and chronically activate the innate immune system.

This pro-inflammatory state leads to physiological senescence of CNS cells. Once CNS cells undergo physiological senescence, they secrete a variety of pro-inflammatory molecules.

Thus, the senescence of cells, which wasinitially triggered by inflammatory stimuli, becomes a self-reinforcing stimulus for further inflammation and senescence. Ultimately, senescent CNS cells become functionally impaired and eventually die, and this neurodegeneration leads to brain organ failure...

lurkingforacure 10-13-2009 08:50 AM

Adding up
 
Additional support for PD's interaction/relationship to immune function. Thanks for finding and sharing this.

olsen 10-13-2009 10:28 AM

hypothesis
 
though just a hypothesis, would make a case for use of immune stimulating agents such as LDN or anti inflammatory agents.

girija 10-13-2009 02:01 PM

Quote:

Originally Posted by olsen (Post 577729)
though just a hypothesis, would make a case for use of immune stimulating agents such as LDN or anti inflammatory agents.

Thanks! This link between immune system and PD is getting stronger and more and more papers are coming out. But still it generates luke warm response (well, not as much as I thought any way) among PD researchers!
Olsen, please check your im!

Thanks'Girija

lindylanka 10-13-2009 06:43 PM

this is one of those theories that seem to have a kind of plausible logic......

my personal feeling is that inflammation and immune response are part of my condition.....

whether this could be a sole cause of PD is another matter, especially when you read of all the drugs and chemicals that are likely suspects.... and the genetic causes - we are both more fragile and tougher than we seem.......


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