Title:Emerging Proof of Protein Misfolding and Interactions in Multifactorial Alzheimer's Disease
VOLUME: 20 ISSUE: 26
Author(s):Md. Sahab Uddin*, Abdullah Al Mamun, Md. Ataur Rahman, Tapan Behl, Asma Perveen, Abdul Hafeez, May N. Bin-Jumah, Mohamed M. Abdel-Daim and Ghulam Md Ashraf*
Affiliation:Department of Pharmacy, Southeast University, Dhaka, Department of Pharmacy, Southeast University, Dhaka, Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology, Seoul, Chitkara College of Pharmacy, Chitkara University, Punjab, Glocal School of Life Sciences, Glocal University, Saharanpur, Glocal School of Pharmacy, Glocal University, Saharanpur, Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh 11474, Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, King Fahd Medical Research Center, King Abdulaziz University, Jeddah
Keywords:Aβ, Tau, Protein misfolding, Protein interaction, Neurotoxicity, Alzheimer's disease.
Abstract:
Objective: Alzheimer's disease (AD) is a devastating neurodegenerative disorder, characterized
by the extracellular accumulations of amyloid beta (Aβ) as senile plaques and intracellular aggregations
of tau in the form of neurofibrillary tangles (NFTs) in specific brain regions. In this review, we
focus on the interaction of Aβ and tau with cytosolic proteins and several cell organelles as well as associated
neurotoxicity in AD.
Summary: Misfolded proteins present in cells accompanied by correctly folded, intermediately folded,
as well as unfolded species. Misfolded proteins can be degraded or refolded properly with the aid of
chaperone proteins, which are playing a pivotal role in protein folding, trafficking as well as intermediate
stabilization in healthy cells. The continuous aggregation of misfolded proteins in the absence of
their proper clearance could result in amyloid disease including AD. The neuropathological changes of
AD brain include the atypical cellular accumulation of misfolded proteins as well as the loss of neurons
and synapses in the cerebral cortex and certain subcortical regions. The mechanism of neurodegeneration
in AD that leads to severe neuronal cell death and memory dysfunctions is not completely understood
until now.
Conclusion: Examining the impact, as well as the consequences of protein misfolding, could help to
uncover the molecular etiologies behind the complicated AD pathogenesis.
