Mitochondrial dysfunction in sleep deprivation.

Insufficient sleep gradually elevates oxidative stress and impairs mitochondrial function. Both oxidative stress and mitochondrial dysfunction are critical factors in the pathology of neurodegenerative disorders. Prolonged sleep deprivation SD ultimately leads to an imbalance of normal cellular processes and an overproduction of reactive oxygen species. The detrimental compounds can damage fat molecules, proteins, and even DNA, and, as a result, intracellular mitochondria, which produce energy, become dysfunctional, leading to reduced ATP production and further compromising the energy supply. Neurons are particularly susceptible to low energy and oxidative stress, which, in turn, increases the risk to the brain. Among the impacts of sleep deprivation are the exacerbation of core symptoms of Parkinson’s disease (PD) and Alzheimer’s disease (AD), such as irregular protein accumulation and neurocommunication deficits. Mitochondrial pathophysiology is closely linked to various brain disorders. The brain requires a specialised form of mitochondrial quality control called mitophagy. Interestingly, mitophagy is less efficient in older individuals or those with chronic sleep deprivation. The accumulation of unprocessed mitochondria exacerbates oxidative stress while further depleting energy-storing substrates. In Parkinson’s disease, the involvement of the PINK1 and Parkin genes, which play roles in mitophagy, underscores the link between mitochondrial clearance failure and the progression of pathological processes. In the context of Alzheimer’s Disease (AD), the lack of mitophagy has been associated with the buildup of amyloid-beta and tau proteins. Considering the contribution of sleep to the brain’s housekeeping functions, one could hypothesise that sleep deprivation could trigger this process in an unhealthy, excessive, or sustained manner, accelerating brain injury. The association of sleep deprivation with mitochondrial dysfunction and neurodegeneration highlights the importance of sleep for the health of the brain. Reductions in oxidative stress and improvements in neuronal energy levels are likely with the restoration of sleep and increased mitophagy. Given that mitochondrial health is of paramount importance in the ageing process and the development of several diseases, including Parkinson’s and Alzheimer’s disease, there is growing interest in the use of antioxidants and drugs that promote mitophagy in these conditions.