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Phosphorylated Smad 2/3 colocalizes with phospho-tau inclusions in Pick disease, progressive supranuclear palsy, and corticobasal degeneration but not with alpha-synuclein inclusions in multiple system atrophy or dementia with Lewy bodies.
J Neuropathol Exp Neurol. 2007 Nov; 66(11):1019-26.JN

Abstract

Impaired transduction of transforming growth factor-beta signaling has recently been implicated in Alzheimer disease. Transforming growth factor-beta signals are transduced by Smads, which are phosphorylated and translocated to the nucleus, where they initiate gene transcription. In Alzheimer disease, neurofibrillary tangles sequester phosphorylated Smad 2/3 (pSmad2/3) and reduce its nuclear translocation. We have now investigated the relationship between pSmad2/3 and phospho-tau in 3 other tauopathies, Pick disease, progressive supranuclear palsy, and corticobasal degeneration, and in 2 alpha-synucleinopathies, dementia with Lewy bodies and multiple system atrophy. In Pick disease, progressive supranuclear palsy, and corticobasal degeneration, pSmad2/3 was demonstrated in neuronal and glial nuclei but also colocalized with cytoplasmic tau inclusions. No pSmad2/3 was detected in glial cytoplasmic inclusions in multiple system atrophy or in Lewy bodies in dementia with Lewy bodies. Our data indicate that phospho-tau but not alpha-synuclein cytoplasmic inclusions bind pSmad2/3. The preservation of neuronal nuclear pSmad2/3 in Pick disease, progressive supranuclear palsy, and corticobasal degeneration suggests that cytoplasmic sequestration of pSmad2/3 is likely to have less impact on transforming growth factor-beta signal transduction in these diseases than in Alzheimer disease.

Authors+Show Affiliations

Dementia Research Group, University of Bristol Institute of Clinical Neurosciences, Department of Clinical Science at North Bristol, Frenchay Hospital, Bristol, BS16 1LE, UK.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17984683

Citation

Chalmers, Katy A., and Seth Love. "Phosphorylated Smad 2/3 Colocalizes With Phospho-tau Inclusions in Pick Disease, Progressive Supranuclear Palsy, and Corticobasal Degeneration but Not With Alpha-synuclein Inclusions in Multiple System Atrophy or Dementia With Lewy Bodies." Journal of Neuropathology and Experimental Neurology, vol. 66, no. 11, 2007, pp. 1019-26.
Chalmers KA, Love S. Phosphorylated Smad 2/3 colocalizes with phospho-tau inclusions in Pick disease, progressive supranuclear palsy, and corticobasal degeneration but not with alpha-synuclein inclusions in multiple system atrophy or dementia with Lewy bodies. J Neuropathol Exp Neurol. 2007;66(11):1019-26.
Chalmers, K. A., & Love, S. (2007). Phosphorylated Smad 2/3 colocalizes with phospho-tau inclusions in Pick disease, progressive supranuclear palsy, and corticobasal degeneration but not with alpha-synuclein inclusions in multiple system atrophy or dementia with Lewy bodies. Journal of Neuropathology and Experimental Neurology, 66(11), 1019-26.
Chalmers KA, Love S. Phosphorylated Smad 2/3 Colocalizes With Phospho-tau Inclusions in Pick Disease, Progressive Supranuclear Palsy, and Corticobasal Degeneration but Not With Alpha-synuclein Inclusions in Multiple System Atrophy or Dementia With Lewy Bodies. J Neuropathol Exp Neurol. 2007;66(11):1019-26. PubMed PMID: 17984683.
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TY - JOUR T1 - Phosphorylated Smad 2/3 colocalizes with phospho-tau inclusions in Pick disease, progressive supranuclear palsy, and corticobasal degeneration but not with alpha-synuclein inclusions in multiple system atrophy or dementia with Lewy bodies. AU - Chalmers,Katy A, AU - Love,Seth, PY - 2007/11/7/pubmed PY - 2007/12/14/medline PY - 2007/11/7/entrez SP - 1019 EP - 26 JF - Journal of neuropathology and experimental neurology JO - J Neuropathol Exp Neurol VL - 66 IS - 11 N2 - Impaired transduction of transforming growth factor-beta signaling has recently been implicated in Alzheimer disease. Transforming growth factor-beta signals are transduced by Smads, which are phosphorylated and translocated to the nucleus, where they initiate gene transcription. In Alzheimer disease, neurofibrillary tangles sequester phosphorylated Smad 2/3 (pSmad2/3) and reduce its nuclear translocation. We have now investigated the relationship between pSmad2/3 and phospho-tau in 3 other tauopathies, Pick disease, progressive supranuclear palsy, and corticobasal degeneration, and in 2 alpha-synucleinopathies, dementia with Lewy bodies and multiple system atrophy. In Pick disease, progressive supranuclear palsy, and corticobasal degeneration, pSmad2/3 was demonstrated in neuronal and glial nuclei but also colocalized with cytoplasmic tau inclusions. No pSmad2/3 was detected in glial cytoplasmic inclusions in multiple system atrophy or in Lewy bodies in dementia with Lewy bodies. Our data indicate that phospho-tau but not alpha-synuclein cytoplasmic inclusions bind pSmad2/3. The preservation of neuronal nuclear pSmad2/3 in Pick disease, progressive supranuclear palsy, and corticobasal degeneration suggests that cytoplasmic sequestration of pSmad2/3 is likely to have less impact on transforming growth factor-beta signal transduction in these diseases than in Alzheimer disease. SN - 0022-3069 UR - https://www.unboundmedicine.com/medline/citation/17984683/Phosphorylated_Smad_2/3_colocalizes_with_phospho_tau_inclusions_in_Pick_disease_progressive_supranuclear_palsy_and_corticobasal_degeneration_but_not_with_alpha_synuclein_inclusions_in_multiple_system_atrophy_or_dementia_with_Lewy_bodies_ L2 - https://academic.oup.com/jnen/article-lookup/doi/10.1097/nen.0b013e31815885ad DB - PRIME DP - Unbound Medicine ER -