Mitophagy: A promising therapeutic target for neuroprotection during ageing and age‐related diseases

Abstract

Mitochondria and mitochondria-mediated signalling pathways are known to control synaptic signalling, as well as long-lasting changes in neuronal structure and function.Mitochondrial impairment is linked to synaptic dysfunction in normal ageing and age-associated neurodegenerative ailments, including Parkinson's disease (PD) and Alzheimer's disease (AD). Both proteolysis and mitophagy perform a major role in neuroprotection, by maintaining a healthy mitochondrial population during ageing.Mitophagy, a highly evolutionarily conserved cellular process, helps in the clearance of damaged mitochondria and thereby maintains the mitochondrial and metabolic balance, energy supply, neuronal survival and neuronal health. Besides the maintenance of brain homeostasis, hippocampal mitophagy also helps in synapse formation, axonal development, dopamine release and long-term depression. In contrast, defective mitophagy contributes to ageing and age-related neurodegeneration by promoting the accumulation of damaged mitochondria leading to cellular dysfunction.Exercise, stress management, maintaining healthy mitochondrial dynamics and administering natural or synthetic pharmacological compounds are some of the strategies used for neuroprotection during ageing and age-related neurological diseases.The current review discusses the impact of defective mitophagy in ageing and ageassociated neurodegenerative conditions, the underlying molecular pathways and potential therapies based on recently elucidated mitophagy-inducing strategies.

Targeting mitochondrial dynamics of morphine-responsive dopaminergic neurons ameliorates opiate withdrawal

“…The clearance of damaged mitochondria by mitophagy plays a fundamental role in mitochondrial function and metabolic homeostasis in neurons ( 38 , 39 ). A mitochondria-targeting Keima (mt-Keima), a pH-sensitive dual-excitation fluorescent protein, was expressed in the VTA neurons.…”

Berberine Rescues D-Ribose-Induced Alzheimer‘s Pathology via Promoting Mitophagy

“…An abundant literature links the modulation of autophagy to altered Alzheimer’s pathogenesis [ 38 , 39 ]. Mitophagy, a specialized form of macroautophagy, selectively degrades damaged and dysfunctional mitochondria which contribute to normal aging and a wide spectrum of age-related diseases [ 40 ], including Parkinson’s disease and Alzheimer’s disease [ 41 , 42 ]. Hence, maintaining a healthy mitophagy status in aged individuals might be a beneficial strategy.…”

Advancements in the study of synaptic plasticity and mitochondrial autophagy relationship

“…Facilitating mitochondrial autophagy helps eliminate damaged mitochondria, thereby maintaining brain homeostasis, including mitochondrial and metabolic balance, energy supply, neuronal survival, and neural health (Itoh et al., 2013; Kageyama et al., 2012; Misgeld & Schwarz, 2017; Vives‐Bauza et al., 2010). Additionally, normal mitochondrial autophagy contributes to processes such as synaptic formation and axonal development (Mishra & Thakur, 2023). Research suggests that glucocorticoids reduce mitochondrial autophagy and inhibit anterograde transport.…”