Title:A Comprehensive Review of Alzheimer’s Association with Related Proteins: Pathological Role and Therapeutic Significance
Volume: 18
Issue: 8
Author(s): Deepak Kumar, Aditi Sharma and Lalit Sharma*
Affiliation:
- School of Pharmaceutical Sciences, Shoolini University, Solan, H.P.,India
Keywords:
Alzheimer`s, neurodegeneration, proteins, pathological role, therapeutics.
Abstract: Alzheimer’s is an insidious, progressive, chronic neurodegenerative disease which causes
the devastation of neurons. Alzheimer's possesses complex pathologies of heterogeneous nature
counting proteins as one major factor along with enzymes and mutated genes. Proteins such as amyloid
precursor protein (APP), apolipoprotein E (ApoE), presenilin, mortalin, calbindin-D28K, creactive
protein, heat shock proteins (HSPs), and prion protein are some of the chief elements in the
foremost hypotheses of AD like amyloid-beta (Aβ) cascade hypothesis, tau hypothesis, cholinergic
neuron damage, etc. Disturbed expression of these proteins results in synaptic dysfunction, cognitive
impairment, memory loss, and neuronal degradation. On the therapeutic ground, attempts of
developing anti-amyloid, anti-inflammatory, anti-tau therapies are on peak, having APP and tau as
putative targets. Some proteins, e.g., HSPs, which ameliorate oxidative stress, calpains, which help
in regulating synaptic plasticity, and calmodulin-like skin protein (CLSP) with its neuroprotective
role are few promising future targets for developing anti-AD therapies. On diagnostic grounds of
AD C-reactive protein, pentraxins, collapsin response mediator protein-2, and growth-associated
protein-43 represent the future of new possible biomarkers for diagnosing AD. The last few decades
were concentrated over identifying and studying protein targets of AD. Here, we reviewed the
physiological/pathological roles and therapeutic significance of nearly all the proteins associated
with AD that addresses putative as well as probable targets for developing effective anti-AD therapies.