The enzyme asparagine endopeptidase (AEP) mediates pathologic activity in PD & AD
 

"A particular chunk of alpha-synuclein produced by AEP's scissors can be found in samples of brain tissue from patients with PD, but not in control samples ..."

"The researchers also observed that the chunk of alpha-synuclein generated by AEP is more likely to aggregate into clumps than the full length protein ..."

Emory press release:
Drug discovery: Alzheimer's and Parkinson's spurred by same enzyme | Emory University | Atlanta, GA

Research paper:
Asparagine endopeptidase cleaves alpha-synuclein and mediates pathologic activities in Parkinson's disease, Zhentao Zhang et al., Nature Structural & Molecular Biology, July 3 2017.
Asparagine endopeptidase cleaves α-synuclein and mediates pathologic activities in Parkinson's disease (PDF Download Available)

Thanks jeffreyn.

I know about AEP as its δ-secretase synonym in the context of AD but it would never have occurred to me that it might cleave α-synuclein as well.

Though there is much more work to do, this could be a big step forward in treatment of both AD and PD, especially as candidate inhibitors of AED have been found.

Coincidence?

"Asparagine endopeptidase cleaves α-synuclein and mediates pathologic activities in Parkinson's disease"

"Fructose-asparagine is a glycosylamine compound that is used during Salmonella-mediated inflammation of the intestine."
Fructose-asparagine - Wikipedia

A post by Rick Everett:

https://www.neurotalk.org/parkinson-...ght=salmonella

pointed me to this:

"Acute Neuronal and Systemic Inflammation caused by
Lipopolysaccharides of Salmonella minnesota can be
stopped by treatment with the Antibiotic Ofloxacin"
Inflammation of the human central nervous system caused by Salmonella minnesota S-LPS can be stopped by the quinolone ofloxacin

[Rick was the star contributor to this forum. He died in 2014. He is sadly missed.]

John

I'd be happy to be proven wrong, but at this stage my money is on "coincidence".

I think that it probably is a coincidence.

Asparagine is an amino acid which is found in almost all proteins. What the recent papers show is that AEP can cleave two proteins (Amyloid Precursor Protein and Tau) at specific asparagine residues, which promotes formation of neurotoxic species in AD and the same applies to cleavage of α-synuclein by AEP in PD.

Although fructose-asparagine is inflammatory I don't know if it can enter the brain. If it can I would expect it to have systemic effects rather than specific effects as in PD and AD though I could be wrong about this.