Alzheimer's Disease
Alzheimer’s Disease (AD) is a progressive neurological disorder that causes the brain to shrink and neurons to die. The hallmarks of AD are amyloid plaques and neurofibrillary tangles formed by uncontrolled aggregation of Aβ and Tau protein.
The amyloid precursor protein is cleaved by β and ɣ secretase and forms the Aβ fragment, which then accumulates and aggregates, thus injuring neurons and synapses. The plaques are mainly present in the regions responsible for memory and cognitive functions.
Various post-translational modifications (PTMs) in Aβ are reported and shown to enhance Aβ aggregation propensity additionally. PTMs can function as a molecular switch to evoke cellular response or could trigger pathological pathways leading to disease progression. Till date there is no systematic study on PTM enabled Aβ. The existing drug based therapeutics have not considered PTM enabled Aβ hence many have failed the clinical trials. Some of the PTMs found in Aβ are racemization, isomerization, phosphorylation, nitration, oxidation, glycosylation, pyro-glutamylation, dityrosine crosslinks.
The existing therapeutic approach for AD only provide symptomatic relief. Till date there are seven FDA approved drug which are able to cure the symptoms of AD and not the condition itself. In the recent decade, peptide-based therapeutics are also being explored, but they have limitations in crossing the blood-brain barrier. Here we are investigating the inhibitory property of peptides on PTM enabled Aβ.
Natural product based therapeutics are studied based on their protein inhibitory activity. The natural products which are able to inhibit the aggregation of Aβ peptide and PTM enabled Aβ aggregation are still under investigation.
