Distinct destructive signal pathways of neuronal death in Alzheimer's disease.
Abundant neuron loss is a major feature of Alzheimer's disease (AD). Hypotheses for this loss include abnormal amyloid precursor protein processing (i.e. excess Abeta production, protein aggregation or misfolding), oxidative stress, excitotoxicity and inflammation. Neuron loss is a major cause of dementia in AD; however, it seems that there is no definitive pathway that causes cell death in the AD brain. Here, we examine the hypotheses for neuron loss in AD and pose the argument that the means by which neurons degenerate is irrelevant for cognitive decline. The best treatment for cognitive decline is to prevent the toxicity that first sets the neuron on its path to destruction, which is the production of Abeta peptide.
Shen
Yong
Y
Haldeman Laboratory of Molecular and Cellular Neurobiology, Sun Health Research Institute 3501, West Santa Fe Drive, Sun City, AZ 85351, USA. yong.shen@sunhealth.org
He
Ping
P
Zhong
Zhenyu
Z
McAllister
Carrie
C
Lindholm
Kristina
K
D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology* / Q000523:psychology; D020013:Calcium Signaling; D002453:Cell Cycle; D016923:Cell Death; D003071:Cognition; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D017628:Microglia / Q000473:pathology / Q000502:physiology; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000502:physiology; D009474:Neurons / Q000473:pathology* / Q000502:physiology; D018384:Oxidative Stress; D017510:Protein Folding; D053218:Receptors, Death Domain / Q000502:physiology; D017470:Receptors, Glutamate / Q000502:physiology; D015398:Signal Transduction
D009419:Nerve Tissue Proteins; D053218:Receptors, Death Domain; D017470:Receptors, Glutamate