Emerging neuroprotective strategies for Alzheimer's disease: dietary restriction, telomerase activation, and stem cell therapy.
The molecular, biochemical and cellular events that result in synaptic dysfunction and neuronal degeneration in the brain in Alzheimer's disease (AD) are becoming known. Age-related increases in cellular oxidative stress, and impairment of energy metabolism, result in disruption of neuronal calcium homeostasis and increased vulnerability of neurons to excitotoxicity and apoptosis. Inherited forms of AD that result from mutations in the beta-amyloid precursor protein (APP) and presenilins accelerate the neurodegenerative cascade by increasing production and deposition of neurotoxic forms of amyloid beta-peptide and by perturbing calcium homeostasis. Dietary restriction (DR; reduced calorie intake with maintained nutrition) extends life span of rodents and (probably) humans. DR increases resistance of neurons to dysfunction and degeneration, and improves behavioral outcome, in experimental models of AD and other age-related neurodegenerative disorders by a mechanism involving a mild stress response. Telomerase, a specialized reverse transcriptase, has been proposed to possess anti-aging properties. The catalytic subunit of telomerase (TERT) is expressed in neurons throughout the brain during development, but is absent from neurons in the adult brain. TERT exhibits neuroprotective properties in experimental models of neurodegenerative disorders suggesting that manipulations that induce telomerase in neurons may protect against age-related neurodegeneration. Finally, the exciting and exploding field of stem cell research suggests methods for replacing damaged or lost brain cells in an array of neurological disorders.
Mattson
M P
MP
Laboratory of Neurosciences - 4F01, National Institute on Aging, 5600 Nathan Shock Drive, Baltimore, MD 23224, USA. mattsonm@grc.nia.nih.gov
D000544:Alzheimer Disease / Q000178:diet therapy* / Q000201:enzymology / Q000517:prevention & control / Q000628:therapy*; D004789:Enzyme Activation; D006801:Humans; D009462:Neurology / Q000639:trends; D033581:Stem Cell Transplantation; D019098:Telomerase / Q000378:metabolism*
D019098:Telomerase