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CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Intervention of Proliferation and Differentiation of Endogenous Neural Stem Cells in the Neurodegenerative Process of Huntingtons Disease Phenotype

Author(s): Yvona Mazurova, Ivana Guncova, Ivan Latr and Emil Rudolf

Volume 10 , Issue 4 , 2011

Page: [486 - 499] Pages: 14

DOI: 10.2174/187152711795563967

Price: $65

Abstract

The evidence for the existence of neurogenesis in the adult mammalian brain, including humans is now widely accepted. Despite the fact that adult neural stem cells appear to be very promising, a wide range of their unrevealed properties, abilities but also limitations under physiological and especially pathological conditions still need to be investigated and explained. Huntingtons disease (HD) is characterized by successive degeneration of relatively well-defined neuronal population. Moreover, the most affected region, the caudate nucleus, is adjacent to the subependymal zone (SEZ) neurogenic region. Therefore, the possibility to harness the endogenous neural stem cell capacity for repairing, or at least restricting, the fatal neurodegenerative process in HD patients using promoted neurogenesis in the adult SEZ represent the exciting new possibility in clinical management of this disorder. On the other hand, many questions have to be answered before neuronal replacement therapies using endogenous precursors become a reality, particularly in relation to neurodegenerative diseases. Fundamental for all experimental, functional and future clinical studies is detailed morphological description of structures involved in the process of neurogenesis. The objectives of this review are to describe neurogenesis in the adult murine and human brain (with particular emphasis to morphological aspects of this process) and to determine to what extent it is affected in animal models of HD and in the human HD brain. Due to very limited evidence referring to the impact of striatal pathology of HD phenotype on the adult neurogenesis in the SEZ, some results gained from our studies on two rat models of HD, i.e. the neurotoxic lesion and transgenic HD rats, and on human HD brains are discussed.

Keywords: Adult neurogenesis, neural stem cells, subependymal zone, Huntington's disease, neurotoxin-induced model, transgenic HD rats, histopathology, parkinson's disease, alzheimer's disease, PCNA, neurotoxin-induced models, transgenic murine rodent models, GFAP, PSA-NCAM


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