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Patterns of protein nitration in dementia with Lewy bodies and striatonigral degeneration.
Acta Neuropathol. 2002 May; 103(5):495-500.AN

Abstract

The synucleinopathies are a group of neurodegenerative disorders characterized by the presence of alpha-synuclein inclusions in neurons (Lewy body diseases, LBD) or glial cells (multiple system atrophies, MSA). Recently, nitration of alpha-synuclein has been reported as the possible modification that induces its aggregation and deposition in these disorders. In this study we investigated the distribution and relationships of alpha-synuclein inclusions and 3-nitrotyrosine (3-NT), a marker of protein nitration through oxidative mechanisms, in brains diagnosed with LBD or MSA and control brains using double immunohistochemical techniques. In LBD cases, 3-NT colocalized with alpha-synuclein immunoreactivity in classic and cortical Lewy bodies and in dystrophic neurites in substantia nigra. However, most pale bodies and diffuse deposits in substantia nigra and Lewy neurites in hippocampus lack 3-NT immunoreactivity. A majority of cases showed diffuse cytoplasmic 3-NT staining in pyramidal cells of the CA2-3 regions of the hippocampus that was independent of alpha-synuclein deposits. All MSA cases showed 3-NT immunoreactivity in glial inclusions. 3-NT neuronal staining was restricted to pontine nuclei with three cases showing nuclear and one case cytoplasmic staining. There was no colocalization of 3-NT nuclear immunoreactivity with alpha-synuclein-immunopositive nuclear inclusions in pontine neurons. These data show that protein nitration in LBD and MSA cases has a widespread distribution and is not only associated with the alpha-synuclein deposits. The presence of alpha-synuclein-positive deposits lacking 3-NT immunoreactivity suggests that nitration is not a prerequisite for alpha-synuclein deposition.

Authors+Show Affiliations

Servicio de Neurología, Fundación Jiménez Díaz and Banco de Tejidos para Investigación Neurológica, Universidad Complutense, 28040 Madrid, Spain. egomezt@fjd.esNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

11935266

Citation

Gómez-Tortosa, Estrella, et al. "Patterns of Protein Nitration in Dementia With Lewy Bodies and Striatonigral Degeneration." Acta Neuropathologica, vol. 103, no. 5, 2002, pp. 495-500.
Gómez-Tortosa E, Gonzalo I, Newell K, et al. Patterns of protein nitration in dementia with Lewy bodies and striatonigral degeneration. Acta Neuropathol. 2002;103(5):495-500.
Gómez-Tortosa, E., Gonzalo, I., Newell, K., García Yébenes, J., Vonsattel, P., & Hyman, B. T. (2002). Patterns of protein nitration in dementia with Lewy bodies and striatonigral degeneration. Acta Neuropathologica, 103(5), 495-500.
Gómez-Tortosa E, et al. Patterns of Protein Nitration in Dementia With Lewy Bodies and Striatonigral Degeneration. Acta Neuropathol. 2002;103(5):495-500. PubMed PMID: 11935266.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Patterns of protein nitration in dementia with Lewy bodies and striatonigral degeneration. AU - Gómez-Tortosa,Estrella, AU - Gonzalo,Isabel, AU - Newell,Kathy, AU - García Yébenes,Justo, AU - Vonsattel,Paul, AU - Hyman,Bradley T, Y1 - 2002/02/23/ PY - 2001/07/18/received PY - 2001/10/15/revised PY - 2001/10/31/accepted PY - 2002/4/6/pubmed PY - 2002/6/22/medline PY - 2002/4/6/entrez SP - 495 EP - 500 JF - Acta neuropathologica JO - Acta Neuropathol VL - 103 IS - 5 N2 - The synucleinopathies are a group of neurodegenerative disorders characterized by the presence of alpha-synuclein inclusions in neurons (Lewy body diseases, LBD) or glial cells (multiple system atrophies, MSA). Recently, nitration of alpha-synuclein has been reported as the possible modification that induces its aggregation and deposition in these disorders. In this study we investigated the distribution and relationships of alpha-synuclein inclusions and 3-nitrotyrosine (3-NT), a marker of protein nitration through oxidative mechanisms, in brains diagnosed with LBD or MSA and control brains using double immunohistochemical techniques. In LBD cases, 3-NT colocalized with alpha-synuclein immunoreactivity in classic and cortical Lewy bodies and in dystrophic neurites in substantia nigra. However, most pale bodies and diffuse deposits in substantia nigra and Lewy neurites in hippocampus lack 3-NT immunoreactivity. A majority of cases showed diffuse cytoplasmic 3-NT staining in pyramidal cells of the CA2-3 regions of the hippocampus that was independent of alpha-synuclein deposits. All MSA cases showed 3-NT immunoreactivity in glial inclusions. 3-NT neuronal staining was restricted to pontine nuclei with three cases showing nuclear and one case cytoplasmic staining. There was no colocalization of 3-NT nuclear immunoreactivity with alpha-synuclein-immunopositive nuclear inclusions in pontine neurons. These data show that protein nitration in LBD and MSA cases has a widespread distribution and is not only associated with the alpha-synuclein deposits. The presence of alpha-synuclein-positive deposits lacking 3-NT immunoreactivity suggests that nitration is not a prerequisite for alpha-synuclein deposition. SN - 0001-6322 UR - https://www.unboundmedicine.com/medline/citation/11935266/Patterns_of_protein_nitration_in_dementia_with_Lewy_bodies_and_striatonigral_degeneration_ L2 - https://dx.doi.org/10.1007/s00401-001-0495-3 DB - PRIME DP - Unbound Medicine ER -