Abstract:

Glutamate (Glu) is the main excitatory amino acid in the brain and plays a pivotal role in many neurophysiological functions. Nevertheless, an excess and prolonged exposure to Glu determines the overactivation of glutamate receptors (GluRs) with consequent impairment of cellular calcium (Ca2+) homeostasis, leading to the dysregulation of intracellular pathways and resulting in neuronal dysfunction and death, a process called excitotoxicity. In the last two decades, excitotox mechanisms have been proposed to explain the neuronal cell death characteristic of neurodegenerative diseases such as Huntington’s, Alzheimer’s and Parkinson’s disease, including increase of intracellular Ca2+, accumulation of oxidizing free radicals, impairment of mitochondrial function and activation of apoptotic and autophagic programs. Since excitotoxicity is implicated in a variety of neuropathological conditions it represents a common pathogenic pathway for neurodegenerative diseases with distinct genetic etiologies and it appears to be important in determining the extent of tissue damage.
Dr. Clotilde Lauro (Sapienza University of Rome, Italy) showed that in the attempt to counteract excitotoxic insult, damaged neurons respond by releasing soluble factors that might be sensed by surrounding cells to induce a wide range of cellular responses leading to neuroprotection and tissue damage repair. Among these factors there is fractalkine (CX3CL1), a chemokine constitutively expressed on neuronal membrane that is upregulated, cleaved and released upon excitotoxic insult.