Journal
CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
Volume 20, Issue 1, Pages 54-67Publisher
BENTHAM SCIENCE PUBL
DOI: 10.2174/1871527319666200903162200
Keywords
Neurodegenerative diseases; post-translational modification; neuronal dysfunction; phosphorylation; acetylation; palmitoylation; SUMOylation; ubiquitination
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Funding
- Indian Council of Medical Research [45/48/2019-PHA/BMS, 45/19/2018-NANO/BMS]
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Neurodegenerative diseases are characterized by detrimental modifications in brain proteins, leading to aggregation, misfolding, and deposition. Post-Translational Modifications (PTM) play crucial roles in regulating protein characteristics, but the underlying mechanisms causing abnormal PTM remain poorly understood. Studying specific disease-associated protein PTM is crucial for evaluating protein functional alterations and their association with neurodegeneration.
Neurodegenerative diseases, including Alzheimer's Disease (AD), Parkinson's Disease (PD), Amyotrophic Lateral Sclerosis (ALS) and Huntington's Disease (HD), are characterized by progressive neuronal dysfunction and death. Recent studies have established detrimental modifications in the structure and function of brain proteins, which stimulate their aggregation, misfolding and deposition in and around the neurons an important hallmark of neurodegenerative diseases. Post-Translational Modification (PTM) of proteins, including phosphorylation, acetylation, glycosylation, palmitoylation, SUMOylation, and ubiquitination, are important regulators of protein characteristics, including stability, intracellular distribution, activity, interactions, aggregation and clearance. Despite clear evidence that altered protein modifications emerging from impromptu chemical modifications to side chains of amino acid are associated with neurodegeneration, the underlying mechanisms that promote aberrant PTM remain poorly understood. Therefore, elucidating PTM of specific disease-associated proteins can prove to be a significant step in evaluating the functional alteration of proteins and their association with neurodegeneration. This review describes how aberrant PTM of various proteins is linked with the neurodegenerative disease pathogenesis, as well as molecular strategies targeting these modifications for treating such diseases, which are yet incurable.
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