Perturbed neuronal calcium homeostasis is a prominent feature in Alzheimer's disease (AD). Mitochondria accumulate calcium ions (Ca2+) for cellular bioenergetic metabolism and suppression of mitochondrial motility within the cell. Excessive Ca2+uptake into mitochondria often leads to mitochondrial membrane permeabilization and induction of apoptosis. Ca2+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 Ca2+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 Ca2+transport pathways. It is reasoned that these mitochondrial Ca2+modulators are most effective in combination with agents that increase the Ca2+buffering capacity of mitochondria. Modulation of mitochondrial Ca2+handling is a potential pharmacological target for future development of AD treatments.
- Alzheimer's disease
- Mitochondrial membrane potential
- Voltage dependent anion channel
ASJC Scopus subject areas
- Molecular Biology