ABSTRACT
Department of Biotechnology and Biosciences, Laboratory of Neuroscience “R. Levi-Montalcini”, University of Milano-Bicocca, 20126 Milan, Italy.
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. Th is chapter aims to give an overview of the essential molecular pathways underlying neuroapoptosis and the complex intracellular and intercellular crosstalks 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 Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD), then the role of mitochondrial dysfunction, alterations of intracellular Ca2+ homeostasis and production of oxidative stress in the induction of neuronal apoptosis are considered. Th e 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, such as amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS) and peripheral neuropathies (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.
