Abstract
Apoptosis plays a major role in shaping the developing nervous system during embryogenesis as neuronal precursors differentiate to become post-mitotic neurons. However, once neurons are incorporated into functional circuits and become mature, they greatly restrict their capacity to die via apoptosis, thus allowing the mature nervous system to persist in a healthy and functional state throughout life. This robust restriction of the apoptotic pathway during neuronal differentiation and maturation is defined by multiple unique mechanisms that function to more precisely control and restrict the intrinsic apoptotic pathway. However, while these mechanisms are necessary for neuronal survival, mature neurons are still capable of activating the apoptotic pathway in certain pathological contexts. In this review, we highlight key mechanisms governing the survival of post-mitotic neurons, while also detailing the physiological and pathological contexts in which neurons are capable of overcoming this high apoptotic threshold.
Original language | English |
---|---|
Pages (from-to) | 3276-3298 |
Number of pages | 23 |
Journal | FEBS Journal |
Volume | 286 |
Issue number | 17 |
Early online date | 23 Jun 2019 |
DOIs | |
Publication status | Published - 1 Sept 2019 |
Bibliographical note
AcknowledgementsWe thank Dr Matt Geden for insightful comments on this manuscript. This work was supported by a grant from National Institutes of Health (GM118331) to MD.
Author contributions
EH and SER wrote the manuscript and MD helped edit the text.
Publisher Copyright:
© 2019 Federation of European Biochemical Societies
Keywords
- Apaf-1
- apoptosis
- Bcl-2
- caspase
- JNK
- neurodegeneration
- neuronal maturation
- neurons
- NPCs
- XIAP