title: In Vivo Profiling Reveals a Competent Heat Shock Response in Adult Neurons: Implications for Neurodegenerative Disorders.
abstract: The heat shock response (HSR) is the main pathway used by cells to counteract proteotoxicity. The inability of differentiated neurons to induce an HSR has been documented in primary neuronal cultures and has been proposed to play a critical role in ageing and neurodegeneration. However, this accepted dogma has not been demonstrated in vivo. We used BAC transgenic mice generated by the Gene Expression Nervous System Atlas project to investigate the capacity of striatal medium sized spiny neurons to induce an HSR as compared to that of astrocytes and oligodendrocytes. We found that all cell populations were competent to induce an HSR upon HSP90 inhibition. We also show the presence and relative abundance of heat shock-related genes and proteins in these striatal cell populations. The identification of a competent HSR in adult neurons supports the development of therapeutics that target the HSR pathway as treatments for neurodegenerative disorders.
authors.affiliation: Dept. Medical and Molecular Genetics, King's College London, 8th Floor Tower Wing, Guy's Hospital, Great Maze Pond, London, SE1 9RT, United Kingdom.
authors.forename: Alisia
authors.initials: A
authors.lastname: Carnemolla
authors.affiliation: Dept. Medical and Molecular Genetics, King's College London, 8th Floor Tower Wing, Guy's Hospital, Great Maze Pond, London, SE1 9RT, United Kingdom.
authors.forename: Hayley
authors.initials: H
authors.lastname: Lazell
authors.affiliation: Novartis Institute for Biomedical Science, Neuroscience Discovery, Basel, CH-4002, Switzerland.
authors.forename: Saliha
authors.initials: S
authors.lastname: Moussaoui
authors.affiliation: Dept. Medical and Molecular Genetics, King's College London, 8th Floor Tower Wing, Guy's Hospital, Great Maze Pond, London, SE1 9RT, United Kingdom.
authors.forename: Gillian P
authors.initials: GP
authors.lastname: Bates
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001253:Astrocytes / Q000166:cytology; D001921:Brain / Q000378:metabolism; D022202:Chromosomes, Artificial, Bacterial; D003342:Corpus Striatum / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D018869:Heat-Shock Response / Q000502:physiology*; D006624:Hippocampus / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D009836:Oligodendroglia / Q000166:cytology; D011728:Pyridones / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: C570862:2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido(4,3-d)pyrimidin-5(6H)-one; D018841:HSP90 Heat-Shock Proteins; D011728:Pyridones; D011743:Pyrimidines; D012333:RNA, Messenger