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IMBB researchers reveal a novel mechanism underlying necrotic neurodegeneration

Dec 14, 2011

Research carried out at the Institute of Molecular Biology and Biotechnology, published today in the international scientific periodical EMBO Journal, reveals a novel molecular mechanism required for the degeneration of nerve cells.

Neurodegenerative disorders, such as Amyotrophic lateral sclerosis, Alzheimer’s, Parkinson’s and Huntington’s diseases are among the most devastating human pathologies, which significantly affect life quality and expectancy. A main hallmark of these pathologies is the gradual loss of neuronal cells in the brain and spinal cord, through necrotic processes. As a consequence of neuron death, patients developsuppo physical and mental impairments (coordination and motility problems, loss of memory and speech defects). Many of these symptoms also arise after stroke or ischemic episodes, where neurons degenerate in a similar manner.

The rapid increase of the incidence of neurodegenerative disorders worldwide makes the development of effective therapeutic strategies a critical priority. However, despite intense research efforts in recent years, many aspects of necrotic cell death are not understood. Elucidation of the mechanisms involved in necrosis is essential for the development of novel intervention approaches for prevention, delay or treatment of neurodegenerative pathologies.

By using the simple nematode worm Caenorhabditis elegans, the IMBB researchers, Kostoula Troullinaki and Nektarios Tavernarakis revealed that two processes essential cell processes, endocytosis and intracellular trafficking, also contribute to necrotic cell death. Endocytosis is important for the import of nutrients and various molecules from the cell surface that will then processed inside the cell. Particularly in neurons, endocytosis is critical for the integration and transmission of signals to other neurons. In addition, trafficking of different cargoes intracellularly, to their proper location is vital for the normal function of the cell. The two IMBB researchers have found that hyperactivation of these processes, under certain pathological conditions becomes detrimental, contributing to cell destruction. Moreover, the scientists have shown that these processes synergize with other mechanisms implicated in necrosis, such as autophagy and lysosomal proteolysis, to facilitate neurodegeneration. Inhibition of these processes protects neurons from cell death induced by many different insults.

Characterization of the involvement of endocytosis and intracellular trafficking in neuronal loss sheds light into the molecular mechanisms responsible for necrotic cell death and is likely to facilitate the discovery of educated intervention strategies for the prevention or amelioration of neurodegenerative disorders.

For more information please contact:
Prof. Nektarios Tavernarakis, Research Director
(Tel.: +30 2810391066; Email: tavernarakis@imbb.forth.gr)
Relevant links: http://www.elegans.gr/ & http://www.nature.com/emboj/index.html

Endocytosis and intracellular trafficking contribute to necrotic neurodegeneration in C. elegan (pdf.)