Modulation of mitochondrial calcium as a pharmacological target for Alzheimer's disease
Clara Hiu-Ling Hung1, Yuen-Shan Ho, Raymond Chuen-Chung Chang
1Laboratory of Neurodegenerative Diseases, Department of Anatomy, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
Abstract:
Perturbed neuronal calcium homeostasis is a prominent feature in Alzheimer's disease (AD). Mitochondria accumulate calcium ions (Ca(2+)) for cellular bioenergetic metabolism and suppression of mitochondrial motility within the cell. Excessive Ca(2+) uptake into mitochondria often leads to mitochondrial membrane permeabilization and induction of apoptosis. Ca(2+) is an interesting second messenger which can initiate both cellular life and death pathways in mitochondria. This review critically discusses the potential of manipulating mitochondrial Ca(2+) concentrations as a novel therapeutic opportunity for treating AD. This review also highlights the neuroprotective role of a number of currently available agents that modulate different mitochondrial Ca(2+) transport pathways. It is reasoned that these mitochondrial Ca(2+) modulators are most effective in combination with agents that increase the Ca(2+) buffering capacity of mitochondria. Modulation of mitochondrial Ca(2+) handling is a potential pharmacological target for future development of AD treatments.
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