TMM review: Mitophagy and Neuroprotection

Congratulations to postdocs Guofeng Lou and Sofie Lautrup for their fresh Ópinion´ review paper in the Trends in Molecular Medicine

Highlights

  • Mitophagy, an evolutionally conserved cellular self-degradation of damaged mitochondria, is impaired in major neurodegenerative diseases, including AD, PD, ALS, FTD, and HD.
  • Defective mitophagy in postmortem brain samples from AD patients and in AD animal models is caused by several mechanisms, including by the inhibition of the ULK1/TBK1-dependent initiation of the mitophagic machinery via Tau/Aβ proteinopathies.
  • In mice and rhesus monkeys, PINK1 deletion does not induce significant mitophagy impairment at physiological conditions, suggesting a compensatory response by other mitophagy pathways. Studies in the rhesus monkeys also suggest the existence of none–mitophagy–regulatory role(s) of PINK1.
  • Therapeutic strategies targeting on mitophagy induction ameliorate disease pathology and inhibit neuronal loss in both AD and PD mouse models.

Abstract

Neurodegenerative diseases are strongly age-related and currently cannot be cured, with a surge of patient numbers in the coming decades in view of the emerging worldwide ageing population, bringing healthcare and socioeconomic challenges. Effective therapies are urgently needed, and are dependent on new aetiological mechanisms. In neurons, efficient clearance of damaged mitochondria, through the highly evolutionary conserved cellular process termed mitophagy, plays a fundamental role in mitochondrial and metabolic homeostasis, energy supply, neuronal survival, and health. Conversely, defective mitophagy leads to accumulation of damaged mitochondria and cellular dysfunction, contributing to ageing and age-predisposed neurodegeneration. Here, we discuss the contribution of defective mitophagy in these diseases, and underlying molecular mechanisms, and highlight novel therapeutics based on new discovered mitophagy-inducing strategies.

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Written by noage100

A Norwegian integrated, interdisciplinary, world-class centre for human ageing research

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