Trends in Neurosciences
ViewpointMechanisms underlying neural cell death in neurodegenerative diseases: alterations of a developmentally-mediated cellular rheostat
Section snippets
Regulation of regional neurogenesis and abnormalities in associated developmental processes that predispose to cell death
The mechanisms governing the genesis of regional neuronal subtypes are still largely unknown. There is increasing recognition that the elaboration and maintenance of these regional neuronal subpopulations are determined by the interplay of soluble signals, gradient morphogens and transcriptional regulators that are expressed during progressive stages of neural induction, patterning of the neuraxis and neurogenesis and endow these evolving subpopulations with unique cellular properties24 (Fig. 1
Role of presenilin mutations in altering the viability and cellular homeostasis of neural developmental species
Impairments in the cellular homeostasis of mutant neural precursor and mature neuronal species may be mediated by a variety of developmental mechanisms (Fig. 2). PS1 directly interacts with anti-apoptotic bcl2 family members that normally preserve the viability of neural stem/progenitor (bcl2) and nascent neuroblast (bcl-xL) subpopulations during sequential stages of developmental apoptosis42., 43.. PS1–/– mice exhibit massive neuronal death during embryonic stages of neurogenesis, whereas
Acknowledgements
The authors thank B. Shapiro for artistic expertise, R. Sanchez for performing the protein database searches and K.S. Marder and Z. Kaprielian for critical commentaries. The authors research was supported by grants from the NINDS, NIH. We sincerely regret the fact that space limitations have prevented us from citing the many outstanding experimental studies that have contributed to our evolving view of the relationship between development and neurodegeneration.
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2020, NeuroImage: ClinicalCitation Excerpt :Importantly, two recent in vivo studies of global anthropometric measures in asymptomatic subjects carrying the mutated gene also point at a developmental aspect in HD (Nopoulos et al., 2011; Lee et al., 2012). These are, to our knowledge, the only human studies showing results supporting the thought-provoking idea that degeneration in some disorders of possible genetic aetiology, including HD and Alzheimer's disease, might be the consequence of abnormal development, with certain populations of neuronal cells made more vulnerable to late life stressors (Mehler and Gokhan, 2000; Molero et al., 2009; Marder and Mehler, 2012). Here, we carried out for the first time in HD a sulcal morphometry analysis using a tool that automatically reconstructs and labels sulci from T1-weighted images (Riviere et al., 2002; Mangin et al., 2004).
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