Role of apoptosis in the pathogenesis of Parkinson's disease: A novel therapeutic opportunity?

✍ Scribed by Ilan Ziv; Eldad Melamed

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 594 KB
• Volume: 13
• Category: Article
• ISSN: 0885-3185
• DOI: 10.1002/mds.870130602

✦ Synopsis

The cause of the selective degeneration of nigrostriatal neurons in Parkinson's disease (PD) is still enigmatic. However, the last several years since the introduction of the concept of apoptosis have been characterized by exciting advances that may shed light on the process of the neuronal death underlying this common neurologic disorder.

Apoptosis (programmed cell death, PCD) is an active, genetically controlled program of cell self-demise or "suicide," which is inherent in every cell.'z2 When receiving an appropriate signal, cells undergo a dramatic and highly characteristic chain of biochemical and morphologic events, with cell shrinkage, loss of contacts with neighboring cells, formation of membrane blebs on the cell surface, massive cytoskeletal re-arrangements, accompanied by chromatin condensation and DNA fragmentation at internucleosomal sites. Apoptotic cells are ultimately converted to clusters of membrane-bound particles (apoptotic bodies), which are engulfed by neighboring macro phage^.^ Three major steps are now recognized in this death p r o ~e s s ' ~~, ~: ( I ) The triggering stimulus: Numerous triggers of apoptosis are now known, ranging from DNA damage, cell cycle perturbations, metabolic or toxic insults, deprivation of growth factors, to activation of specific cell death receptors. These triggers converge to activate central cell death signals, that lead to the (2) Apoptosis commitment point: the point of no return beyond