NMR studies of amyloid .beta.-peptides: proton assignments, secondary structure, and mechanism of an .alpha.-helix .fwdarw. .beta.-sheet conversion for a homologous, 28-residue, N-terminal fragment

Biochemistry ◽  
1992 ◽  
Vol 31 (24) ◽  
pp. 5621-5631 ◽  
Author(s):  
Michael G. Zagorski ◽  
Colin J. Barrow
Keyword(s):  
Secondary Structure ◽  
Amyloid Beta ◽  
Alpha Helix ◽  
Beta Sheet ◽  
Nmr Studies ◽  
Amyloid Beta Peptides ◽  
Beta Peptides ◽  
Terminal Fragment

Amyloid beta peptides and glutamatergic synaptic dysregulation

2008 ◽  
Vol 210 (1) ◽  
pp. 7-13 ◽  
Author(s):  
Kodeeswaran Parameshwaran ◽  
Muralikrishnan Dhanasekaran ◽  
Vishnu Suppiramaniam
Keyword(s):  
Amyloid Beta ◽  
Amyloid Beta Peptides ◽  
Beta Peptides

Deferoxamine reduces amyloid-beta peptides genesis and alleviates neural apoptosis after traumatic brain injury

Neuroreport ◽  
2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Wang-Dui Zhaba ◽  
Qu-Zhen Deji ◽  
Sheng-Qing Gao ◽  
Yan-Ling Han ◽  
Chao-Chao Gao ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Amyloid Beta ◽  
Amyloid Beta Peptides ◽  
Beta Peptides ◽  
Neural Apoptosis

scholarly journals The orphan drug dichloroacetate reduces amyloid beta-peptide production whilst promoting non-amyloidogenic proteolysis of the amyloid precursor protein

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0255715
Author(s):  
Edward T. Parkin ◽  
Jessica E. Hammond ◽  
Lauren Owens ◽  
Matthew D. Hodges
Keyword(s):  
Amyloid Precursor Protein ◽  
Orphan Drug ◽  
Amyloid Beta ◽  
Precursor Protein ◽  
Amyloid Beta Peptide ◽  
Amyloid Beta Peptides ◽  
Over Expression ◽  
Beta Peptides ◽  
Amyloidogenic Processing ◽  
Beta Peptide

The amyloid cascade hypothesis proposes that excessive accumulation of amyloid beta-peptides is the initiating event in Alzheimer’s disease. These neurotoxic peptides are generated from the amyloid precursor protein via sequential cleavage by β- and γ-secretases in the ’amyloidogenic’ proteolytic pathway. Alternatively, the amyloid precursor protein can be processed via the ’non-amyloidogenic’ pathway which, through the action of the α-secretase a disintegrin and metalloproteinase (ADAM) 10, both precludes amyloid beta-peptide formation and has the additional benefit of generating a neuroprotective soluble amyloid precursor protein fragment, sAPPα. In the current study, we investigated whether the orphan drug, dichloroacetate, could alter amyloid precursor protein proteolysis. In SH-SY5Y neuroblastoma cells, dichloroacetate enhanced sAPPα generation whilst inhibiting β–secretase processing of endogenous amyloid precursor protein and the subsequent generation of amyloid beta-peptides. Over-expression of the amyloid precursor protein partly ablated the effect of dichloroacetate on amyloidogenic and non-amyloidogenic processing whilst over-expression of the β-secretase only ablated the effect on amyloidogenic processing. Similar enhancement of ADAM-mediated amyloid precursor protein processing by dichloroacetate was observed in unrelated cell lines and the effect was not exclusive to the amyloid precursor protein as an ADAM substrate, as indicated by dichloroacetate-enhanced proteolysis of the Notch ligand, Jagged1. Despite altering proteolysis of the amyloid precursor protein, dichloroacetate did not significantly affect the expression/activity of α-, β- or γ-secretases. In conclusion, dichloroacetate can inhibit amyloidogenic and promote non-amyloidogenic proteolysis of the amyloid precursor protein. Given the small size and blood-brain-barrier permeability of the drug, further research into its mechanism of action with respect to APP proteolysis may lead to the development of therapies for slowing the progression of Alzheimer’s disease.

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