Abstract
The cellular and molecular mechanisms underlying the reciprocal relationship between adult neurogenesis, cognitive and motor functions have been an important focus of investigation in the establishment of effective neural replacement therapies for neurodegenerative disorders. While neuronal loss, reactive gliosis and defects in the self-repair capacity have extensively been characterized in neurodegenerative disorders, the transient excess production of neuroblasts detected in the adult striatum of animal models of Huntington’s disease (HD) and in post-mortem brain of HD patients, has only marginally been addressed. This abnormal cellular response in the striatum appears to originate from the selective proliferation and ectopic migration of neuroblasts derived from the subventricular zone (SVZ). Based on and in line with the term “reactive astrogliosis”, we propose to name the observed cellular event “reactive neuroblastosis”. Although, the functional relevance of reactive neuroblastosis is unknown, we speculate that this process may provide support for the tissue regeneration in compensating the structural and physiological functions of the striatum in lieu of aging or of the neurodegenerative process. Thus, in this review article, we comprehend different possibilities for the regulation of striatal neurogenesis, neuroblastosis and their functional relevance in the context of HD.
Highlights
Huntington’s disease (HD) is an adult onset, progressive neurodegenerative syndrome that has clinically been characterized by chorea, dementia and psychiatric illness (Walker, 2007)
It has been predicted that recent advancements in CRISPR/Cas9 genome-editing tools and patient-specific generation of induced pluripotent stem cells might significantly contribute to the development of future gene therapies for HD (Xu et al, 2017)
The subventricular zone (SVZ) continues to harbor a heterogeneous population of neural stem cells (NSCs) that generates polarized neuroblast progenies, migrating through the rostral migratory stream (RMS) into the olfactory bulb (OB), where they terminally mature into functional interneurons (Doetsch et al, 1997, 1999; Gritti et al, 2002; Ming and Song, 2011)
Summary
Huntington’s disease (HD) is an adult onset, progressive neurodegenerative syndrome that has clinically been characterized by chorea, dementia and psychiatric illness (Walker, 2007). Reactive Neuroblastosis in Huntington’s Disease gene (The Huntington’s Disease Collaborative Research Group, 1993). The unstable CAG repeat expansion of more than 35–39 in the HD gene is translated into polyglutamine (polyQ) stretches in the huntingtin protein (Bates, 2003; Cornett et al, 2005; Moily et al, 2014). The abnormal polyQ repeat sequence is known to cause misfolding and aggregation of the huntingtin protein (DiFiglia et al, 1997; Bates, 2005; Poirier et al, 2005) leading to the selective degeneration of medium spiny neurons (MSNs) in the striatum and onset of the disease (Graveland et al, 1985). Refining mechanisms of the existing self-regenerative process of the adult brain, namely adult neurogenesis, holds great promise for the establishment of non-invasive clinical procedures to treat HD
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