Title:Comprehensive Perspective Towards the Management of Proteinopathies
by Elucidating Protein Misfolding and Aggregation
Volume: 23
Issue: 2
Author(s): Ishfaq Ahmad Ahanger, Ghulam Md. Ashraf*, Anurag Sharma*Asimul Islam*
Affiliation:
- Department of Medical Laboratory Sciences, College of Health Science, and Sharjah Institute of
Medical Research, University of Sharjah, Sharjah, United Arab Emirates
- Department of Chemistry,
Biochemistry, and Forensic Science, Amity School of Applied Sciences, Amity University Haryana, Gurugram 122 413,
Haryana, India
- Centre for Interdisciplinary
Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India
Keywords:
Protein aggregation, generic propensity, proteinopathies, neurodegenerative diseases, protein folding landscape, protein quality control.
Abstract: Protein misfolding and aggregation is the phenomenon of the generic propensity of proteins,
considered as a dark side of the protein world, and its exact mechanism is still not deciphered.
Understanding the complexity of protein aggregation is currently the primary apprehension and challenge
in biology and medicine due to their association with various debilitating human proteinopathies
and neurodegenerative diseases. The mechanism of protein aggregation, associated diseases, and the
development of efficient therapeutic strategies against these diseases are very challenging. These diseases
are caused by different proteins, each protein with different mechanisms and consisting of various
microscopic phases or events. These microscopic steps are functioning on different timescales during
aggregation. Here, we highlighted the different features and current trends in protein aggregation.
The study thoroughly recapitulates the various factors influencing, possible causes, types of aggregates
and aggregation, their different proposed mechanisms, and the methods used to study the aggregation.
Additionally, the formation and elimination of misfolded or aggregated proteins in the cell, the role of
the ruggedness of the protein folding landscape in protein aggregation, proteinopathies, and the challenges
for their prevention are comprehensively elucidated. A holistic understanding of different aspects
of aggregation, molecular steps governing the various features of protein quality control, and
crucial queries about the modulation of these processes and their interactions with other systems in
cellular protein quality control can be considered conducive to comprehending the mechanism, designing
effective approaches towards prevention of protein aggregation, rationalizing the etiology and development
of novel strategies against therapy and management of the proteinopathies.
