Abstract
Neurodegenerative disorders like Alzheimer’s, Parkinson’s, Huntington’s and ALS; present a complex biological disorder resulting loss of synaptic connections, neuronal damage and decay in old and elderly persons. Such a degrading process of neurons affects the central nervous system and results in loss of cognitive abilities, memory, sensory abilities and impairs the motor neuron functions. Thus, understanding the biology of neurodegenerative diseases has been crucial in ensuring healthy aged life. Although several cases of familial neurodegenerative disorders have been reported, yet the mechanism for sporadic neuronal degeneration remains largely unknown. Therefore, in this review we aim to understand the role of environmental triggers, i.e. epigenetics in affecting the normal functioning and coordination of host nervous system. A distinct signature mark of neurodegenerative disorders involves misfolding and structural aberration in native proteins leading to formation of intracellular fibrillary tangles, Lewy bodies, extracellular plaques, to name a few. This paper focusses primarily on four kinds of neurodegenerative disorders as mentioned above and reviewed the role of DNA/histone methylation, acetylation, ubiquitination along with mutational changes to the native protein product.
Highlights
Neurodegeneration usually refers to a progressive impairment of the structure and function of nerve cells leading to their damage and death
Alzheimer’s patients exhibit altered 5 mc levels in the brain and lymphocytes along with altered expression of genes like APOE and PSEN1, DNA methyltransferase-1 (DNMT1) and methylenetetrahydrofolate reductase (MTHFR- required for methylation homeostasis) (Figure 2)
Clinical studies aimed at treatment of Alzheimer’s have affirmed a possible approach wherein in vitro or dietary administration of the components required for production of S- adenosylmethionine (SAM) like folate, homocysteine and B - group vitamins can be utilized to restore methylation levels of PSEN1, protract brain atrophy and minimize oxidative stress (Figure 3) [76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94]
Summary
Neurodegeneration usually refers to a progressive impairment of the structure and function of nerve cells leading to their damage and death. The consequences of such neurodegenerative processes are usually observed as loss in motor neuron functions, impaired sensory abilities, decline in memory and cognitive abilities along with hindrances in functioning of several organs and organ systems. Some of the common neurodegenerative disorders include alzheimer’s disease, Parkinson’s disease, Huntington’s disease and a comparatively rarer condition called Amyotrophic Lateral Sclerosis (ALS). These comprise the most prominent nervous disorders amongst the rest. It becomes highly imperative to understand the disease biology, identify unique signature marks and look for molecules and structural entities associated with such diseases to develop an effective remedy targeted against neurodegenerative disorders
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