The role of mitochondrial disturbances in Alzheimer, Parkinson and Huntington diseases

Abstract

Mitochondria are highly dynamic organelles involved in a multitude of cellular events. Disturbances of mitochondrial function and dynamics are associated with cells degeneration and death. Neurons, perhaps more than any other cell, depend on mitochondria for their survival. In fact, accumulating evidence reveals that mitochondria take center stage in several neurodegenerative diseases. Here we will give an overview of the mechanisms involved in the maintenance of a healthy mitochondrial pool in neuronal cells and how disturbances in these processes underlie the pathophysiology of three common neurodegenerative disorders, Alzheimer, Parkinson and Huntington diseases. Additionally, we will discuss the role of sirtuins in neurodegeneration and how mitohormesis and vitagenes activation may counteract neurodegenerative events.

Keywords:

• Alzheimer disease
• Huntington disease
• mitochondrial abnormalities
• mitohormesis
• Parkinson disease
• sirtuins
• vitagenes

Financial & competing interests disclosure

C Carvalho received a technician fellowship from Alzheimer Association. P Moreira was supported by Quadro de Referência Estratégico Nacional. S Correia, S Cardoso, E Candeias, A Placido and A Duarte all received fellowships from Portuguese Foundation for Science and Technology. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Neurodegenerative diseases, including Alzheimer disease (AD), Parkinson disease (PD) and Huntington disease (HD), are characterized by mitochondrial dysfunction.

• Defects in mitochondrial fission–fusion contribute to neurodegeneration.

• AD, PD and HD are also characterized by altered mitochondrial biogenesis and autophagy.

• Because neurons are highly polarized cells, the impairment of mitochondrial trafficking plays a key role in neurodegeneration.

• Sirtuins have been implicated in several neurodegenerative diseases including AD, PD and HD.

• Improving knowledge about mitochondrial defects in neurodegenerative diseases is expected to have profound implications for developing new treatments for these diseases.

• Mitohormesis and activation of vitagenes may represent feasible strategies to fight neurodegenerative diseases.

Notes