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Relationship among alpha-synuclein accumulation, dopamine synthesis, and neurodegeneration in Parkinson disease substantia nigra.
J Neuropathol Exp Neurol. 2006 Aug; 65(8):808-15.JN

Abstract

The histologic hallmark of Parkinson disease (PD) is loss of pigmented neurons in the substantia nigra (SN) and locus ceruleus (LC) with accumulation of alpha-synuclein (alphaS). It has been reported that tyrosine hydroxylase (TH)-negative pigmented neurons are present in these nuclei of patients with PD. However, the relationship between TH immunoreactivity and alphaS accumulation remains uncertain. We immunohistochemically examined the SN and LC from patients with PD (n = 10) and control subjects (n = 7). A correlation study indicated a close relationship among decreased TH immunoreactivity, alphaS accumulation, and neuronal loss. In addition, 10% of pigmented neurons in the SN and 54.9% of those in the LC contained abnormal alphaS aggregates. Moreover, 82.3% of pigmented neurons bearing alphaS aggregates in the SN and 39.2% of those in the LC lacked TH immunoreactivity, suggesting that pigmented neurons in the SN have a greater tendency to lack TH activity than those in the LC. Recent studies have shown that this decrease of TH activity leads to a decrease of cytotoxic substances and that decreased dopamine synthesis leads to a reduction of cytotoxic alphaS oligomers. Therefore, the decrease of TH immunoreactivity in pigmented neurons demonstrated here can be considered to represent a cytoprotective mechanism in PD.

Authors+Show Affiliations

Department of Neuropathology, Institute of Brain Science, Hirosaki University School of Medicine, Japan.No 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

Language

eng

PubMed ID

16896314

Citation

Mori, Fumiaki, et al. "Relationship Among Alpha-synuclein Accumulation, Dopamine Synthesis, and Neurodegeneration in Parkinson Disease Substantia Nigra." Journal of Neuropathology and Experimental Neurology, vol. 65, no. 8, 2006, pp. 808-15.
Mori F, Nishie M, Kakita A, et al. Relationship among alpha-synuclein accumulation, dopamine synthesis, and neurodegeneration in Parkinson disease substantia nigra. J Neuropathol Exp Neurol. 2006;65(8):808-15.
Mori, F., Nishie, M., Kakita, A., Yoshimoto, M., Takahashi, H., & Wakabayashi, K. (2006). Relationship among alpha-synuclein accumulation, dopamine synthesis, and neurodegeneration in Parkinson disease substantia nigra. Journal of Neuropathology and Experimental Neurology, 65(8), 808-15.
Mori F, et al. Relationship Among Alpha-synuclein Accumulation, Dopamine Synthesis, and Neurodegeneration in Parkinson Disease Substantia Nigra. J Neuropathol Exp Neurol. 2006;65(8):808-15. PubMed PMID: 16896314.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Relationship among alpha-synuclein accumulation, dopamine synthesis, and neurodegeneration in Parkinson disease substantia nigra. AU - Mori,Fumiaki, AU - Nishie,Makoto, AU - Kakita,Akiyoshi, AU - Yoshimoto,Makoto, AU - Takahashi,Hitoshi, AU - Wakabayashi,Koichi, PY - 2006/8/10/pubmed PY - 2006/9/16/medline PY - 2006/8/10/entrez SP - 808 EP - 15 JF - Journal of neuropathology and experimental neurology JO - J Neuropathol Exp Neurol VL - 65 IS - 8 N2 - The histologic hallmark of Parkinson disease (PD) is loss of pigmented neurons in the substantia nigra (SN) and locus ceruleus (LC) with accumulation of alpha-synuclein (alphaS). It has been reported that tyrosine hydroxylase (TH)-negative pigmented neurons are present in these nuclei of patients with PD. However, the relationship between TH immunoreactivity and alphaS accumulation remains uncertain. We immunohistochemically examined the SN and LC from patients with PD (n = 10) and control subjects (n = 7). A correlation study indicated a close relationship among decreased TH immunoreactivity, alphaS accumulation, and neuronal loss. In addition, 10% of pigmented neurons in the SN and 54.9% of those in the LC contained abnormal alphaS aggregates. Moreover, 82.3% of pigmented neurons bearing alphaS aggregates in the SN and 39.2% of those in the LC lacked TH immunoreactivity, suggesting that pigmented neurons in the SN have a greater tendency to lack TH activity than those in the LC. Recent studies have shown that this decrease of TH activity leads to a decrease of cytotoxic substances and that decreased dopamine synthesis leads to a reduction of cytotoxic alphaS oligomers. Therefore, the decrease of TH immunoreactivity in pigmented neurons demonstrated here can be considered to represent a cytoprotective mechanism in PD. SN - 0022-3069 UR - https://www.unboundmedicine.com/medline/citation/16896314/Relationship_among_alpha_synuclein_accumulation_dopamine_synthesis_and_neurodegeneration_in_Parkinson_disease_substantia_nigra_ L2 - https://academic.oup.com/jnen/article-lookup/doi/10.1097/01.jnen.0000230520.47768.1a DB - PRIME DP - Unbound Medicine ER -