PPARGC1A and early-onset autosomal dominant Alzheimer disease: In addition, other PGC- 1 alpha stimulating factors, such as nitric oxide and estrogen, could be positively regulated by exercise (60–63), and this could be helpful to increase the mitochondrial biogenesis through PGC- 1 alpha for restoring synaptic functions in neurodegenerative diseases such as Parkinson`s and Alzheimer’s diseases (18).