Localization of MAP1-LC3 in Vulnerable Neurons and Lewy Bodies in Brains of Patients With Dementia With Lewy Bodies
| Autor: | Michiko Minegishi, Omi Katsuse, Heii Arai, Kiyoshi Sato, Keiji Wada, Darren J. Moore, Takashi Togo, Hiroshige Fujishiro, Kenji Kosaka, Yoshiko Furukawa, Eizo Iseki, Shinji Higashi, Koji Kasanuki, Hirotake Uchikado, Tomohiro Kabuta, Hiroaki Hino |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Nervous system Pathology Dementia with Lewy bodies Fluorescent Antibody Technique Cell Count Chaperone-Mediated Autophagy Pathogenesis chemistry.chemical_compound Endosome Entorhinal Cortex Alzheimers-Disease Aged 80 and over Neurons Brain Neurofibrillary Tangles General Medicine Middle Aged Immunohistochemistry Lysosome medicine.anatomical_structure Neurology alpha-Synuclein Female Alzheimer's disease Microtubule-Associated Proteins Mutations Plasmids Adult Lewy Body Disease medicine.medical_specialty Mutant Alpha-Synuclein Cells Blotting Western Biology Amygdala Pathology and Forensic Medicine Cellular and Molecular Neuroscience Alzheimer Disease Lysosomal-Associated Membrane Protein 2 mental disorders Autophagy medicine Humans Aged Alpha-synuclein Amyloid beta-Peptides Ubiquitin Protein Lysosome-Associated Membrane Glycoproteins rab7 GTP-Binding Proteins Colocalization medicine.disease Entorhinal cortex Familial Parkinsons-Disease Nervous-System HEK293 Cells chemistry rab GTP-Binding Proteins Lc3 Lewy Bodies Neurology (clinical) Neuroscience |
| Zdroj: | Journal of Neuropathology & Experimental Neurology. 70:264-280 |
| ISSN: | 1554-6578 0022-3069 |
| DOI: | 10.1097/nen.0b013e318211c86a |
| Popis: | There is emerging evidence implicating a role for the autophagy-lysosome pathway in the pathogenesis of Lewy body disease. We investigated potential neuropathologic and biochemical alterations of autophagy-lysosome pathway-related proteins in the brains of patients with dementia with Lewy bodies (DLB), Alzheimer disease (AD), and control subjects using antibodies against Ras-related protein Rab-7B (Rab7B), lysosomal-associated membrane protein 2 (LAMP2), and microtubule-associated protein 1A/1B light chain 3 (LC3). In DLB, but not in control brains, there were large Rab7B-immunoreactive endosomal granules. LC3 immunoreactivity was increased in vulnerable areas of DLB brains relative to that in control brains; computerized cell counting analysis revealed that LC3 levels were greater in the entorhinal cortex and amygdala of DLB brains than in controls. Rab7B levels were increased, and LAMP2 levels were decreased in the entorhinal cortex of DLB brains. In contrast, only a decrease in LAMP2 levels versus controls was found in AD brains. LC3 widely colocalized with several types of Lewy pathology; LAMP2 localized to the periphery or outside of brainstem-type Lewy bodies; Rab7B did not colocalize with Lewy pathology. Immunoblot analysis demonstrated specific accumulation of the autophagosomal LC3-II isoform in detergent-insoluble fractions from DLB brains. These results support apotential role for the autophagy-lysosome pathway in the pathogenesis of DLB. |
| Databáze: | OpenAIRE |
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