Summary and Outlook
Mitochondria have diverse functions and properties and could be critically important for the development of human adult-onset neurodegenerative disorders, including AD, PD, and ALS [7]. Structural and biochemical data from studies of human autopsy CNS as well as cell and animal models of these neurodegenerative disorders suggest that mitochondrial dysfunction is a trigger or propagator of neurodegeneration. Novel mechanisms for mitochondriopathy and neurodegeneration could involve the mPTP (Figure 1 and Figure 2). There is precedence for this logic in mouse models of AD [282], multiple sclerosis [493], stroke [494], and ALS [81]. Using ALS as one example, the mPTP actively participates in the mechanisms of motor neuron death in ALS mice in a gender-preferential pattern [81]. Thus, mPTP activation is a possible triggering event for motor neuron degeneration, and motor neuron selective vulnerability in ALS could be related to amount, composition, and trafficking of mitochondria in these cells. Further study of mitochondria in neurons, glial cells, and skeletal myocytes can define new mechanisms of cell death and disease and can lead to the identification of molecular mechanism-based therapies for treating AD, PD, and ALS.