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Identification of G-protein coupled receptor kinase 2 in paired helical filaments and neurofibrillary tangles.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Takahashi, Makio Uchikado, Hirotake Caprotti, Domenico Weidenheim, Karen M. Dickson, Dennis W. Księżak-Reding, Hanna Pasinetti, Giulio Maria |
| Copyright Year | 2006 |
| Abstract | G-protein coupled receptor kinases (GRKs) constitute a serine/threonine kinase family playing a major role in agonist-induced phosphorylation and desensitization of G-protein coupled receptors. Recently, GRK2 and GRK5 have been demonstrated to phosphorylate alpha-synuclein (Ser129) and other synuclein isoforms. We studied colocalization of GRK2, GRK5, alpha-synuclein, and tau in neurodegenerative disorders characterized by fibrillary tau inclusions and/or alpha-synuclein-enriched Lewy bodies. We found that Lewy bodies were negative for both GRK2 and GRK5 in Lewy body disease (LBD) and LBD mixed with Alzheimer disease (AD + LBD). Instead, GRK2 but not GRK5 colocalized with 40% to 50% of neurofibrillary tangles in AD + LBD and AD brains. In disorders with less prominent alpha-synucleinopathy, neuronal and glial fibrillary tau deposits known to contain distinct subsets of tau isoforms were also positive for GRK2. These deposits included tufted astrocytes and coiled bodies in progressive supranuclear palsy, astrocytic plaques in corticobasal degeneration, and Pick bodies in Pick disease. In addition, paired helical filaments isolated from AD and AD + LBD brains were found to immunogold-label for GRK2, suggesting that GRK2 could be a potential tau kinase associated with fibrillary tau. Our studies indicate that GRK2 is a novel component of neuronal and glial fibrillary tau deposits with no preference in tau isoform binding. GRK2 may play a role in hyperphosphorylation of tau in tauopathies. |
| Starting Page | 415 |
| Ending Page | 420 |
| Page Count | 6 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://jnen.oxfordjournals.org/content/jnen/65/12/1157.full.pdf |
| PubMed reference number | 17146290v1 |
| Volume Number | 65 |
| Issue Number | 12 |
| Journal | Journal of neuropathology and experimental neurology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Abducens Nerve Diseases Alzheimer's Disease Beta-Adrenergic Receptor Kinase 1 Brain Corpora paraaortica G-protein coupled receptor kinase activity GRK5 gene Inclusion Bodies Lafora Disease Lewy Bodies Lewy Body Disease MARK2 gene Neurodegenerative Disorders Neurofibrillary degeneration (morphologic abnormality) Neuroglia Parkinson Disease Progressive supranuclear palsy Protein Isoforms Protein-Serine-Threonine Kinases Senile Plaques Synucleins Tau protein:PrThr:Pt:Body fld:Ord Tauopathies Threonine alpha-Mannosidosis alpha-Synuclein corticobasal degeneration eIF-2 Kinase hypersensitivity desensitization |
| Content Type | Text |
| Resource Type | Article |
