[Frontiers in Bioscience, Landmark, 22, 854-872, January 1, 2017]

Mitochondria in the pathophysiology of Alzheimer’s and Parkinson’s diseases

Isaac G. Onyango 1 , Shaharyar M. Khan 1 , James P Bennett Jr 2

1Gencia Biotechnology, 706 B Forest St, Charlottesville, VA 22903 USA, 2Neurodegeneration Therapeutics, 3050 A Berkmar Dr, Charlottesville, VA 22901

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Mitochondrial DNA (mtDNA) mutations in AD and PD
4. Mitochondrial biogenesis
5. Mitochondrial oxidative stress
6. Mitochondria and altered calcium homeostasis
7. Mitophagy
8. Mitochondrial stress response signaling
9. Mitochondria and inflammation
10. Conclusion and perspective
11. References

1. ABSTRACT

Mitochondria are responsible for the majority of energy production in energy-intensive tissues like brain, modulate Ca+2 signaling and control initiation of cell death. Because of their extensive use of oxygen and lack of protective histone proteins, mitochondria are vulnerable to oxidative stress (ROS)-induced damage to their genome (mtDNA), respiratory chain proteins and ROS repair enzymes. Animal and cell models of PD use toxins that impair mitochondrial complex I activity. Maintenance of mitochondrial mass, mitochondrial biogenesis (mitobiogenesis), particularly in high-energy brain, occurs through complex signaling pathways involving the upstream “master regulator” PGC-1alpha that is transcriptionally and post-translationally regulated. Alzheimer disease (AD) and Parkinson disease (PD) brains have reduced respiratory capacity and impaired mitobiogenesis, which could result in beta-amyloid plaques and neurofibrillary tangles. Aggregated proteins in genetic and familial AD and PD brains impair mitochondrial function, and mitochondrial dysfunction is involved in activated neuroinflammation. Mitochondrial ROS can activate signaling pathways that mediate cell death in neurodegenerative diseases. The available data support restoration of mitochondrial function to reduce disease progression and restore lost neuronal function in AD and PD.

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Key Words: Alzheimer’s Disease, Parkinson’s Disease, Mitochondria, Mitophagy, Oxidative Stress, Mitochondrial Biogenesis, Mitochondrial Dynamics, Neuroinflammation, Immunoaging, Review

Send correspondence to: Isaac G. Onyango, GenciaBiotechnology, 706 B Forest St, Charlottesville, VA 22903 USA, Tel: 434-295-4800, Fax: 434-295-4951, E-mail: ionyango@genciabiotech.com