Mitochondrial dysfunction is a trigger of Alzheimer's disease pathophysiology

Paula I. Moreira (1) , Cristina Carvalho (2) , Xiongwei Zhu (3) , Mark A. Smith (3) , George Perry (4)

1 University of Coimbra
2 Department of Zoology – Faculty of Sciences and Technology
3 Department of Pathology
4 UTSA - The University of Texas at San Antonio

Mitochondria are uniquely poised to play a pivotal role in neuronal cell survival or death because they are regulators of both energy metabolism and cell death pathways. Extensive literature exists supporting a role for mitochondrial dysfunction and oxidative damage in the pathogenesis of Alzheimer's disease. This review discusses evidence indicating that mitochondrial dysfunction has an early and preponderant role in Alzheimer's disease. Furthermore, the link between mitochondrial dysfunction and autophagy in Alzheimer's disease is also discussed. As a result of insufficient digestion of oxidatively damaged macromolecules and organelles by autophagy, neurons progressively accumulate lipofuscin that could exacerbate neuronal dysfunction. Since autophagy is the major pathway involved in the degradation of protein aggregates and defective organelles, an intense interest in developing autophagy-related therapies is growing among the scientific community. The final part of this review is devoted to discuss autophagy as a potential target of therapeutic interventions in Alzheimer's disease pathophysiology.

Mots clés: Alzheimer's disease; autophagy; mitochondria; oxidative stress

Paula I. Moreira, Cristina Carvalho, Xiongwei Zhu, Mark A. Smith, George Perry. Mitochondrial dysfunction is a trigger of Alzheimer's disease pathophysiology. Biochimica et Biophysica Acta - Molecular Basis of Disease, 2009, 1802 (1), pp.2. ⟨10.1016/j.bbadis.2009.10.006⟩. ⟨hal-00562942⟩