When neurogenesis encounters aging and disease.
In this review, we consider the evidence that a reduction in neurogenesis underlies aging-related cognitive deficits and impairments in disorders such as Alzheimer's disease (AD). The molecular and cellular alterations associated with impaired neurogenesis in the aging brain are discussed. Dysfunction of presenilin-1, misprocessing of amyloid precursor protein and toxic effects of hyperphosphorylated tau and β-amyloid probably contribute to impaired neurogenesis in AD. Because factors such as exercise, environmental enrichment and dietary energy restriction enhance neurogenesis, and protect against age-related cognitive decline and AD, knowledge of the underlying neurogenic signaling pathways could lead to novel therapeutic strategies for preserving brain function. In addition, manipulation of endogenous neural stem cells and stem cell transplantation, as stand-alone or adjunct treatments, seems promising.
Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL, USA. olazarov@uic.edu
Orly
O
Lazarov
Mark P
MP
Mattson
Daniel A
DA
Peterson
Sanjay W
SW
Pimplikar
Henriette
H
van Praag
D000375:Aging / Q000502:physiology*; D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D003072:Cognition Disorders / Q000473:pathology / Q000503:physiopathology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D007858:Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology*; D053764:Presenilin-1 / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1