Brain expression level and activity of HDAC6 protein in neurodegenerative dementia |
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| Authors: | Saori Odagiri Kunikazu Tanji Fumiaki Mori Yasuo Miki Akiyoshi Kakita Hitoshi Takahashi Koichi Wakabayashi |
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| Affiliation: | 1. Medical Genetics Unit, IRCCS Casa Sollievo Della Sofferenza Hospital, 71013 San Giovanni Rotondo, Italy;2. Telethon Institute of Genetics and Medicine, Via P. Castellino 111, 80131 Naples, Italy;3. CEINGE Advanced Biotechnology and Department of Organic Chemistry and Biochemistry, Federico II University, 80131 Napoli, Italy;4. Scienze della Riproduzione e dello Sviluppo, University of Trieste, Italy;1. Institute of Neuropathology, Bellvitge University Hospital‐ICS, [Bellvitge Biomedical Research Institute‐] IDIBELL, L’Hospitalet de Llobregat, Spain;2. Departamento de Química Inorgánica, Orgánica y Bioquímica, Facultad de Ciencias y Tecnologías Químicas, Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla-La Mancha, Ciudad Real, Spain;3. Departamento de Química Inorgánica, Orgánica y Bioquímica, Facultad de Medicina de Ciudad Real, CRIB, Universidad de Castilla-La Mancha, Ciudad Real, Spain;4. Departament de Patologia i Terapèutica Experimental, Universitat de Barcelona, L’Hospitalet de Llobregat, Spain;5. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, CIBERNED, Spain;1. Fujian Provincial Key Laboratory of Environmental Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou 350122, China;2. Fujian Provincial Center for Adverse Drug Reaction Monitoring, Fujian Provincial Food and Drug Administration, Fuzhou 350001, China;3. The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, China;4. Deapartment of Mannagement, Fujian Health College, Fuzhou 350101, China;5. Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China;6. Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou 350122, China |
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| Abstract: | Histone deacetylase 6 (HDAC6) is a multifunctional cytoplasmic protein that plays an especially critical role in the formation of aggresomes, where aggregates of excess protein are deposited. Previous immunohistochemical studies have shown that HDAC6 accumulates in Lewy bodies in Parkinson’s disease and dementia with Lewy bodies (DLB) as well as in glial cytoplasmic inclusions in multiple system atrophy (MSA). However, it is uncertain whether the level and activity of HDAC6 are altered in the brains of patients with neurodegenerative dementia. In the present study, we demonstrated that the level of HDAC6 was not altered in the temporal cortex of patients with Alzheimer’s disease and DLB in comparison with controls. In contrast, the level of HDAC6 was significantly increased in the temporal cortex of patients with frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) and in the cerebellar white matter of patients with MSA. However, the level of acetylated α-tubulin, one of the substrates of HDAC6, was not altered in FTLD-TDP and MSA relative to controls. These findings suggest that the induced level of HDAC6 in the brain is insufficient for manifestation of its activity in FTLD-TDP and MSA. |
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