Apoptotic Mechanisms Involved in Neurological Disorders

Apoptosis is a programmed cell death that plays a physiological role during development of the nervous system, while it displays a critical pathological function in chronic neurodegenerative diseases and acute neurological disorders, such as ischemic stroke, epilepsy and brain injury. This review aims to give an overview of the essential molecular pathways underlying neuroapoptosis and the complex intracellular and inter-cellular cross-talks which involve a large number of metabolic and signaling cascades that may also act synergistically during brain damage. Starting from accumulation of damaged/misfolded proteins that mainly characterizes neurodegenerative diseases, such as AD, PD and HD, we then consider the role of mitochondrial dysfunction, alterations of intracellular Ca2+ homeostasis and production of oxidative stress in the induction of neuronal apoptosis. The interplay between neuronal and glial cells is also discussed as a mechanism involved in most neurological conditions including acute (stroke and brain injury) and chronic neurodegenerations (ALS, MS and PNP). Since neuronal-glial network has a role in synaptic plasticity and glutamate metabolism, reactive gliosis may potentiate neuronal death by stimulating glutamate toxicity and disrupting neuronal connections. Finally, we present new insights on molecular mechanisms of neuroprotection, that suggest a new therapeutic strategy for the treatment of several neurological disorders