Mitophagy enhancers as therapeutic targets for neuroprotection against amyloid-beta plaque and neurofibrillary tangle accumulation in Alzheimer’s patients

Amyloid-beta and hyperphosphorylated tau synthesis and accumulation into extraneuronal plaques and intraneuronal neurofibrillary tangles are major contributors to the cellular alterations commonly associated with Alzheimer's disease, including decreased synaptic plasticity, dendritic loss, and neuronal apoptosis. Mitophagy is a crucial mechanism in mitochondrial regulation that involves the selective removal of defective mitochondria by the cell. If this process is impaired, a progressive accumulation of damaged mitochondria and defective organelles may occur. Elevated levels of amyloid-beta, phospho-tau, and various reactive oxygen species, which collectively promote autophagy(definition) and mitophagy, are linked to dysfunctional mitochondria — a pathological hallmark of Alzheimer’s disease and other neurodegenerative disorders. Hence, it has been proposed that the restoration of mitophagy may provide therapeutic benefits to Alzheimer’s patients. In this article, we focus on the potential neuroprotective effects of mitophagy enhancers against the molecular pathologies associated with Alzheimer’s disease, discussing the latest findings and current limitations in this field. The mitophagy enhancers assessed include urolithin A, resveratrol, spermidine, and NAD+.