Abstract
Apoptosis, autophagy and necrosis are the three main types of programmed cell death. One or more of these types of programmed cell death may take place in neurons leading to their death in various neurodegenerative disorders in humans. Purkinje neurons (PNs) are among the most highly vulnerable population of neurons to cell death in response to intrinsic hereditary diseases or extrinsic toxic, hypoxic, ischemic, and traumatic injury. In this review, we will describe the three main types of programmed cell death, including the molecular mechanisms and the sequence of events in each of them, and thus illustrating the intracellular proteins that mediate and regulate each of these types. Then, we will discuss the role of Ca2+ in PN function and increased vulnerability to cell death. Additionally, PN death will be described in animal models, namely lurcher mutant mouse and shaker mutant rat, in order to illustrate the potential therapeutic implications of programmed cell death in PNs by reviewing the previous studies that were carried out to interfere with the programmed cell death in an attempt to rescue PNs from death.
Highlights
Neurodegenerative disorders result from the progressive loss of susceptible populations of neurons [1]
These findings suggested that Bcl-2-associated X protein (Bax) deletion did not permanently inhibit apoptosis but only transiently delayed the degeneration of lurcher Purkinje neurons (PNs) for several weeks [173]
B-cell lymphoma 2 (Bcl-2) overexpression could temporarily delay lurcher PN degeneration Bax deletion only transiently delayed the degeneration of lurcher PNs tissue plasminogen activator (tPA) elimination could delay death receptor-mediated apoptotic pathway and to trigger other apoptotic pathways that were sufficient to elicit PN death Autophagic cell death in granule cells in vitro served as an alternate death pathway, when apoptosis was blocked by caspase inhibition 3-methyladenine inhibition of autophagy in HeLa cell culture triggered apoptotic cell death
Summary
Neurodegenerative disorders result from the progressive loss of susceptible populations of neurons [1]. Neuronal death can occur by one or more of three chief programmed death pathways, which are apoptosis, autophagy, and necrosis [4,5,6]. Apoptosis and autophagy are referred to as programmed cell death type I and type II, respectively [7]. Necrosis has more recently been included as a type of programmed cell death [7, 8]. The vulnerability of cerebellar PNs to cell death will be discussed. PN death in rodent mutants, namely shaker mutant rat and lurcher mutant mouse and the therapeutic implications of the programmed cell death in PNs will be discussed
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
