Update on the association between alpha‐synuclein and tau with mitochondrial dysfunction: Implications for Parkinson's disease

The critical role of mitochondrial dysfunction in the pathological mechanisms of neurodegenerative disorders, particularly Parkinson's disease (PD), is well established. Compelling evidence indicates that Parkinson's proteins (e.g., α‐synuclein, Parkin, PINK1, DJ‐1, and LRRK2) are associated with mitochondrial dysfunction and oxidative stress in PD. Significantly, there is a possible central role of alpha‐synuclein (α‐Syn) in the occurrence of mitochondrial dysfunction and oxidative stress by the mediation of different signaling pathways. Also, tau, traditionally considered as the main component of neurofibrillary tangles, aggregates and amplifies the neurotoxic effects on mitochondria by interacting with α‐Syn. Moreover, oxidative stress caused by mitochondrial dysfunction favors assembly of both α‐Syn and tau and also plays a key role in the formation of protein aggregates. In this review, we provide an overview of the relationship between these two pathological proteins and mitochondrial dysfunction in PD, and also summarize the underlying mechanisms in the interplay of α‐Syn aggregation and phosphorylated tau targeting the mitochondria, to find new strategies to prevent PD processing. Mitochondrial dysfunction and oxidative stress are considered as the pivotal pathomechanisms in Parkinson's disease. More importantly, they also contribute to α‐synuclein aggregation, which is the main pathological feature of Parkinson's disease. Recent advances indicate that α‐synuclein aggregation can interact with tau lesions, thereby disturbing mitochondrial functions and promoting the neurodegenerative process.