title: Connecting Malfunctioning Glial Cells and Brain Degenerative Disorders.
abstract: The DNA damage response (DDR) is a complex biological system activated by different types of DNA damage. Mutations in certain components of the DDR machinery can lead to genomic instability disorders that culminate in tissue degeneration, premature aging, and various types of cancers. Intriguingly, malfunctioning DDR plays a role in the etiology of late onset brain degenerative disorders such as Parkinson's, Alzheimer's, and Huntington's diseases. For many years, brain degenerative disorders were thought to result from aberrant neural death. Here we discuss the evidence that supports our novel hypothesis that brain degenerative diseases involve dysfunction of glial cells (astrocytes, microglia, and oligodendrocytes). Impairment in the functionality of glial cells results in pathological neuro-glial interactions that, in turn, generate a "hostile" environment that impairs the functionality of neuronal cells. These events can lead to systematic neural demise on a scale that appears to be proportional to the severity of the neurological deficit.
authors.affiliation: Department of Neurobiology, George S. Wise, Faculty of Life Sciences, Tel Aviv University, Tel Aviv 6997801, Israel.
authors.forename: Natalie
authors.initials: N
authors.lastname: Kaminsky
authors.affiliation: Department of Neurobiology, George S. Wise, Faculty of Life Sciences, Tel Aviv University, Tel Aviv 6997801, Israel; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 6997801, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Bihari
authors.affiliation: Department of Neurobiology, George S. Wise, Faculty of Life Sciences, Tel Aviv University, Tel Aviv 6997801, Israel. Electronic address: sivankan@gmail.com.
authors.forename: Sivan
authors.initials: S
authors.lastname: Kanner
authors.affiliation: Department of Neurobiology, George S. Wise, Faculty of Life Sciences, Tel Aviv University, Tel Aviv 6997801, Israel; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 6997801, Israel. Electronic address: arib@tauex.tau.ac.il.
authors.forename: Ari
authors.initials: A
authors.lastname: Barzilai
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D064007:Ataxia Telangiectasia Mutated Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D042822:Genomic Instability; D006801:Humans; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D064007:Ataxia Telangiectasia Mutated Proteins
keywords: Astrocytes; Brain degenerative diseases; DNA damage response; Genomic instability; Glial cells; Microglia