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Mortalin Biology: Life, Stress and Death pp 191–207Cite as

Catecholamine Regulated Protein (CRP40), A Splice Variant of Mortalin-2: Functional Role in CNS Disorders

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Abstract

Heat shock proteins are constitutively expressed, but are also induced by heat and other environmental stressors. These proteins play an important role in maintaining correct folding of cellular proteins; protecting the cell from deleterious stresses by inhibiting the aggregation of partially denatured proteins and refolding them to correct confirmations. The Catecholamine Regulated Protein of size 40-kDa (CRP40) is a heat shock-like splice variant of Mortalin-2; its peptide sequence is identical to the carboxyl terminal of Mortalin-2. This protein is found co-localized with tyrosine hydroxylase in the dopaminergic pathways of the midbrain. CRP40 is differentially expressed by dopamine D1 and D2 receptor antagonists; when dopamine concentrations increase, CRP40 is upregulated. Since this increased CRP40 protein expression at high levels of DA is inhibited by treatment of cells with antioxidants, and since the natural oxidation of excess dopamine forms a potent toxic species of oxidant, CRP40 is implicated in the response pathways associated with oxidative stress. Oxidative stress and mitochondrial dysfunction have been implicated in dopaminergic disorders of the brain. CRP40 and Mortalin-2, therefore, are of particularly interest when conducting novel research in the realm of Parkinson’s disease and Schizophrenia. Further, as a splice variant of Mortalin-2, CRP40 could play a central role in research involving other Mortalin-related diseases such as stroke and ischemia, carcinogenesis, Alzheimer’s disease, and Huntington’s disease. With so many unexplored avenues, CRP40 could boast an exciting future in health research.

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Authors and Affiliations

  1. Department of Psychiatry, McMaster University, 1200 Main St. West, HSC 4N81, L8N 3Z5, Hamilton, Canada

    Dr. Joseph P. Gabriele, Sarah E. Groleau, Ritesh P. Daya, Zdenek B. Pristupa & Ram K. Mishra

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  1. Dr. Joseph P. Gabriele
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  2. Sarah E. Groleau
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  3. Ritesh P. Daya
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  4. Zdenek B. Pristupa
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Correspondence to Joseph P. Gabriele .

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  1. National Institute of Advanced Industria, Central 4, Higashi 1 -1-1, Tsukuba, 305 8566, Ibaraki, Japan

    Sunil C. Kaul

  2. Science & Technology (AIST), National Insitute of Advanced Industrial, Central 4, Higashi 1-1-1, Tsukuba, 305-8562, Ibaraki, Japan

    Renu Wadhwa

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Gabriele, J.P., Groleau, S.E., Daya, R.P., Pristupa, Z.B., Mishra, R.K. (2012). Catecholamine Regulated Protein (CRP40), A Splice Variant of Mortalin-2: Functional Role in CNS Disorders. In: Kaul, S., Wadhwa, R. (eds) Mortalin Biology: Life, Stress and Death. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-3027-4_12

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