Abstract
Age-associated neurodegenerative diseases are known to have “impaired protein clearance” as one of the key features causing their onset and progression. Hence, homeostasis is the key to maintaining balance throughout the cellular system as an organism ages. Any imbalance in the protein clearance machinery is responsible for accumulation of unwanted proteins, leading to pathological consequences—manifesting in neurodegeneration and associated debilitating outcomes. Multiple processes are involved in regulating this phenomenon; however, failure to regulate the autophagic machinery is a critical process that hampers the protein clearing pathway, leading to neurodegeneration. Another important and widely known component that plays a role in modulating neurodegeneration is a class of proteins called sirtuins. These are class III histone deacetylases (HDACs) that are known to regulate various vital processes such as longevity, genomic stability, transcription and DNA repair. These enzymes are also known to modulate neurodegeneration in an autophagy-dependent manner. Considering its genetic relevance and ease of studying disease-related endpoints in neurodegeneration, the model system Caenorhabditis elegans has been successfully employed in deciphering various functional outcomes related to critical protein molecules, cell death pathways and their association with ageing. This review summarizes the vital role of sirtuins and autophagy in ageing and neurodegeneration, in particular highlighting the knowledge obtained using the C. elegans model system.
Highlights
The brain is the most complex and a very important part of the body that is responsible for the perfect co-ordination and functioning of other organs
Regarded as self-eating, autophagy is considered to have a protective function in nature, which is very much evident in studies of various model organisms, such as Caenorhabditis elegans and Drosophila, where autophagy upregulation leads to increases in longevity via different mechanisms such as nutrient deprivation, alterations in mitosis and mitochondrial turnover [25]
The regulation of metabolism and homeostasis is a prime necessity for the proper functioning of the body
Summary
The brain is the most complex and a very important part of the body that is responsible for the perfect co-ordination and functioning of other organs. A neuron consists of the cell body that gives way to branches known as dendrites, and axons which help in communicating electric impulses or signals. These impulses are transferred to the neuron via messengers known as neurotransmitters, across the synapse. Research over the past few decades has shed light on fundamental mechanisms associated with age-related diseases; gaps exist in converting mechanistic understanding into translational applications. This makes it imperative to decipher such mechanistic interfaces that allow delving into the prospective aspects of application and translation. The subsequent sections discuss the recent progress in sirtuin-mediated autophagy and its role in age-associated neurodegenerative diseases [6], highlighting the knowledge base that has been generated— from research conducted employing the C. elegans model system
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