Molecular mechanisms of regeneration in Alzheimer's disease brain.
Regenerative responses, including re-expression of developmentally regulated proteins, occur in Alzheimer's disease (AD) brain and in beta-amyloid (Abeta)-treated neuronal cultures. Brain microenvironment might also be altered by Abeta or by unknown materials in AD brain to make neurons or progenitor cells regenerative. However, these responses and alterations might not be sufficient to replace neuronal loss, but rather might act as an effecter of cell death. For instance, downregulation of growth inhibitory factor/metallothionein-III and upregulation of MAP1B result in both neurite sprouting and neuronal death. The deteriorative regulation of Mash1 and Olig2 by Abeta also leads to differentiation and death of progenitor cells. Clarifying the cell death mechanism accompanied with regenerative responses might be necessary for repairing the nervous system or slowing disease progression in AD.
Uchida
Yoko
Y
Tokyo Metropolitan Institute of Gerontology, Itabashiku, Tokyo, Japan. 57uchida@tmig.or.jp
D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D016923:Cell Death / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology; D006131:Growth Inhibitors / Q000502:physiology; D006801:Humans; D000090023:Metallothionein 3; D008869:Microtubule-Associated Proteins / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000502:physiology; D009474:Neurons / Q000502:physiology; D000076104:Oligodendrocyte Transcription Factor 2; D012038:Regeneration
D051792:Basic Helix-Loop-Helix Proteins; D006131:Growth Inhibitors; D000090023:Metallothionein 3; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; C065500:ASCL1 protein, human; C405708:OLIG2 protein, human; C085284:microtubule-associated protein 1B