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Mice expressing the α 1B ‐adrenergic receptor induces a synucleinopathy with excessive tyrosine nitration but decreased phosphorylation
Author(s) -
Papay Robert,
Zuscik Michael J.,
Ross Sean A.,
Yun June,
McCune Dan F.,
GonzalezCabrera Pedro,
Gaivin Robert,
Drazba Judy,
Perez Dianne M.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.01170.x
Subject(s) - neurodegeneration , synucleinopathies , genetically modified mouse , transgene , purkinje cell , tyrosine hydroxylase , microbiology and biotechnology , atrophy , tyrosine , biology , phosphorylation , endocrinology , receptor , medicine , parkinson's disease , chemistry , cerebellum , alpha synuclein , biochemistry , dopamine , disease , gene
We had previously reported that systemic overexpression of the α 1B ‐adrenergic receptor (AR) in a transgenic mouse induced a neurodegenerative disease that resembled the parkinsonian‐like syndrome called multiple system atrophy (MSA). We now report that our mouse model has cytoplasmic inclusion bodies that colocalize with oligodendrocytes and neurons, are positive for α‐synuclein and ubiquitin, and therefore may be classified as a synucleinopathy. α‐Synuclein monomers as well as multimers were present in brain extracts from both normal and transgenic mice. However, similar to human MSA and other synucleinopathies, transgenic mice showed an increase in abnormal aggregated forms of α‐synuclein, which also increased its nitrated content with age. However, the same extracts displayed decreased phosphorylation of α‐synuclein. Other traits particular to MSA such as Purkinje cell loss in the cerebellum and degeneration of the intermediolateral cell columns of the spinal cord also exist in our mouse model but differences still exist between them. Interestingly, long‐term therapy with the α 1 ‐AR antagonist, terazosin, resulted in protection against the symptomatic as well as the neurodegeneration and α‐synuclein inclusion body formation, suggesting that signaling of the α 1B ‐AR is the cause of the pathology. We conclude that overexpression of the α 1B ‐AR can cause a synucleinopathy similar to other parkinsonian syndromes.