Role of microRNAs in neurodegeneration induced by environmental neurotoxicants and aging

Abstract

The progressive loss of neuronal structure and functions resulting in the death of neurons is considered as neurodegeneration. Environmental toxicants induced degeneration of neurons is accelerated with aging. In adult brains, most of the neurons are post-mitotic, and their loss results in the development of diseases like amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington's disease (HD). Neurodegenerative diseases have several similarities at the sub-cellular and molecular levels, such as synaptic degeneration, oxidative stress, inflammation, and cognitive decline, which are also known in brain aging. Identification of these similarities at the molecular level offers hope for the development of new therapeutics to ameliorate all neurodegenerative diseases simultaneously. Aging is known as the most strongly associated additive factor in the pathogenesis of neurodegenerative diseases. Studies carried out so far identified several genes, which are responsible for selective degeneration of neurons in different neurodegenerative diseases. Countless efforts have been made in identifying therapeutics for neurodegenerative diseases; however, the discovery of effective therapy remains elusive. Findings made in the last two decades identified microRNAs (miRNAs) as the most potent post-transcription regulatory RNA molecule, which can condition protein levels in the cell and tissue-specific manner. Identification of miRNAs, which regulate both neurotoxicant and aging-associated degeneration of brain cells, raises the possibility that roads leading to aging and neurotoxicant induced neurodegeneration cross at some point. Identification of miRNAs, which are common to aging and neurotoxicant induced neurodegeneration, will help in understanding the complex mechanism of neurodegenerative disease development. In the future, the use of natural miRNAs in vivo in therapy will be able to tackle several issues of aging and neurodegeneration. In the present review, we have provided a summary of findings made on the role of miRNAs in neurodegeneration and explored the common link made by miRNAs between aging and neurotoxicants induced neurodegeneration.

Keywords: Aging; Neurodegeneration; Neurotoxicants; microRNA.