Optineurin inclusions occur in a minority of TDP-43 positive ALS and FTLD-TDP cases and are rarely observed in otherM neurodegenerative disorders
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Tibor Hortoba´gyi Claire Troakes Agnes L. Nishimura Caroline Vance John C. van Swieten Harro Seelaar Andrew King Safa Al-Sarraj Boris Ro
- چاپ و سال / کشور: 2011
Description
Optineurin (OPTN) is a multifunctional protein involved in vesicular trafficking, signal transduction and gene expression. OPTN mutations were described in eight Japanese patients with familial and sporadic amyotrophic lateral sclerosis (FALS, SALS). OPTN-positive inclusions co-localising with TDP-43 were described in SALS and in FALS with SOD-1 mutations, potentially linking two pathologically distinct pathways of motor neuron degeneration. We have explored the abundance of OPTN inclusions using a range of antibodies in postmortem tissues from 138 cases and controls including sporadic and familial ALS, frontotemporal lobar degeneration (FTLD) and a wide range of neurodegenerative proteinopathies. OPTN-positive inclusions were uncommon and detected in only 11/32 (34%) of TDP-43-positive SALS spinal cord and 5/15 (33%) of FTLD-TDP. Western blot of lysates from FTLD-TDP frontal cortex and TDP-43-positive SALS spinal cord revealed decreased levels of OPTN protein compared to controls (p\0.05), however, this correlated with decreased neuronal numbers in the brain. Large OPTN inclusions were not detected in FALS with SOD-1 and FUS mutation, respectively, or in FTLD-FUS cases. OPTN-positive inclusions were identified in a few Alzheimer’s disease (AD) cases but did not co-localise with tau and TDP-43. Occasional striatal neurons contained granular cytoplasmic OPTN immunopositivity in Huntington’s disease (HD) but were absent in spinocerebellar ataxia type 3. No OPTN inclusions were detected in FTLD-tau and a-synucleinopathy. We conclude that OPTN inclusions are relatively rare and largely restricted to a minority of TDP-43 positive ALS and FTLD-TDP cases. Our results do not support the proposition that OPTN inclusions play a central role in the pathogenesis of ALS, FTLD or any other neurodegenerative disorder.
Acta Neuropathol (2011) 121:519–527r eceived: 19 November 2010 / Revised: 2 February 2011 / Accepted: 16 February 2011 / Published online: 1 March 2011 DOI 10.1007/s00401-011-0813-3
