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Article type: Review Article
Authors: Butterfield, D. Allan; *
Affiliations: Department of Chemistry and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA
Correspondence: [*] Correspondence to: Professor D. Allan Butterfield, Department of Chemistry, University of Kentucky, 506 Rose Street, Lexington, KY 40506, USA. Tel.: +1 859 257 3184; E-mail: [email protected].
Abstract: Activation of cell-cycle machinery in Alzheimer’s disease (AD) brain was reported by Mark Smith and colleagues and by other researchers. Among other biochemical processes underlying this activation, the notion that AD brain, under the onslaught of oxidative and nitrosative damage leading to neuronal loss, neurons would attempt to replenish their numbers by entering the cell cycle. However, being post-mitotic, neurons entering the cell cycle would become trapped therein, ultimately leading to death of these neurons. Yang and co-workers and the Butterfield laboratory first reported that similar activation of the cell cycle was present in the brains of individuals with amnestic mild cognitive impairment (MCI), arguably the earliest clinical stage of AD, but who demonstrate normal activities of daily living and no dementia. Activation of the cell cycle in MCI brain is consonant with the concept that this process is an early aspect in the progression of AD. This brief review article discusses these findings and recognizes the contribution of Dr. Mark Smith to the investigation of cell-cycle activation in AD brain and other aspects of AD neuropathology.
Keywords: Alzheimer’s disease, cell-cycle activation, mild cognitive impairment, oxidative damage, Pin1
DOI: 10.3233/JAD-240615
Journal: Journal of Alzheimer's Disease, vol. 100, no. s1, pp. S277-S281, 2024
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