Genomic Structure and Chromosomal Localization of the Mouse Persyn Gene

Alimova-Kost, Maria V.; Ninkina, Natalia; Imreh, Stefan; Гнучев, Н. В.; Adu, Jimi; Davies, Alun M.; Buchman, Vladimir L.

doi:10.1006/geno.1998.5674

Cited by 4 publications

(2 citation statements)

References 16 publications

(21 reference statements)

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“…2 ␣-Synuclein belongs to an expanding family of synuclein proteins and is homologous to rat and torpedo ␣-synuclein 4 and the zebra finch synelfin. 5 Other members of the synuclein family include ␤-synuclein 6 and ␥-synuclein, or persyn 7,8 and a recently identified protein, synoretin. 9 Recent studies have shown that mutations in the ␣-synuclein gene lead to rare familial forms of Parkinson's disease (PD), a disorder characterized by nigral degeneration and formation of inclusions, denominated Lewy bodies (LBs).…”

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confidence: 99%

α-Synuclein Promotes Mitochondrial Deficit and Oxidative Stress

Hsu

Sagara

Arroyo

et al. 2000

The American Journal of Pathology

646

423

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Abnormal accumulation of the presynaptic protein alpha-synuclein has recently been implicated in the pathogenesis of Alzheimer's and Parkinson's diseases. Because neurodegeneration in these conditions might be associated with mitochondrial dysfunction and oxidative stress, the effects of alpha-synuclein were investigated in a hypothalamic neuronal cell line (GT1-7). alpha-Synuclein overexpression in these cells resulted in formation of alpha-synuclein-immunopositive inclusion-like structures and mitochondrial alterations accompanied by increased levels of free radicals and decreased secretion of gonadotropin-releasing hormone. These alterations were ameliorated by pretreatment with anti-oxidants such as vitamin E. Taken together these results suggest that abnormal accumulation of alpha-synuclein could lead to mitochondrial alterations that may result in oxidative stress and, eventually, cell death.

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mentioning

confidence: 99%

α-Synuclein Promotes Mitochondrial Deficit and Oxidative Stress

Hsu

Sagara

Arroyo

et al. 2000

The American Journal of Pathology

646

423

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“…Mouse and rat β-synuclein are identical and share 97.8% identity with the human protein (Lavedan 1998). The human γ-synuclein gene (SNCG) is located on chromosome 10q23 (Lavedan et al 1998b), whereas the mouse γ-synuclein gene lies on mouse chromosome 14 (Alimova-Kost et al 1999). The human γ-synuclein gene is composed of five exons that encode a 127-amino-acid protein (Lavedan et al 1998b), whereas the mouse γ-synuclein gene encodes a 123-amino-acid protein ( Fig.…”

Section: Synuclein Genes and Proteinsmentioning

confidence: 97%

Synucleins and their relationship to Parkinson’s disease

Halbach

2004

Cell Tissue Res

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Parkinson's disease (PD) is one of the most common neurodegenerative motor disorders, marked by chronic progressive loss of neurons in the substantia nigra. It has long been believed that PD is caused by environmental factors. The discovery of genetic factors involved in PD has improved the understanding of the pathology of the disease. The first gene found to be mutated in PD encodes for the presynaptic protein alpha-synuclein. alpha-Synuclein is a major component of Lewy bodies and Lewy neurites, which represent the morphological hallmarks of the disease. The mechanisms by which alpha-synuclein is involved in nigral cell death remain poorly understood. Moreover, the factors triggering the formation of alpha-synuclein-positive inclusion bodies remain enigmatic. Indeed, even the normal cellular functions of alpha-synuclein and of the other synucleins (beta-synuclein and gamma-synuclein) are still unknown. Several lines of evidence suggest that they play a role in the regulation of vesicular turnover under normal nonpathological conditions.

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Neurons Expressing the Highest Levels of γ-Synuclein Are Unaffected by Targeted Inactivation of the Gene

Ninkina

Papachroni

Robertson

et al. 2003

Molecular and Cellular Biology

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104

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Homologous recombination in ES cells was employed to generate mice with targeted deletion of the first three exons of the ␥-synuclein gene. Complete inactivation of gene expression in null mutant mice was confirmed on the mRNA and protein levels. Null mutant mice are viable, are fertile, and do not display evident phenotypical abnormalities. The effects of ␥-synuclein deficiency on motor and peripheral sensory neurons were studied by various methods in vivo and in vitro. These two types of neurons were selected because they both express high levels of ␥-synuclein from the early stages of mouse embryonic development but later in the development they display different patterns of intracellular compartmentalization of the protein. We found no difference in the number of neurons between wild-type and null mutant animals in several brain stem motor nuclei, in lumbar dorsal root ganglia, and in the trigeminal ganglion. The survival of ␥-synuclein-deficient trigeminal neurons in various culture conditions was not different from that of wild-type neurons. There was no difference in the numbers of myelinated and nonmyelinated fibers in the saphenous nerves of these animals, and sensory reflex thresholds were also intact in ␥-synuclein null mutant mice. Nerve injury led to similar changes in sensory function in wild-type and mutant mice. Taken together, our data suggest that like ␣-synuclein, ␥-synuclein is dispensable for the development and function of the nervous system. Several neurodegenerative diseases have been recently coalesced into a distinct group named synucleinopathies (12,16,20,53). Although they are diverse in symptoms and clinical signs, these diseases share a common histopathological feature, i.e., formation of large intracellular inclusions whose principal component is an aggregated small protein, ␣-synuclein. Neither the normal cellular function of ␣-synuclein nor the exact mechanism of its involvement in neurodegeneration is clearly understood; possible scenarios are discussed in many recent reviews (see, for example, references 10, 28, 33, 34, and 43). Even less clear are the normal functions and roles in neurodegeneration of the other two members of the synuclein family. Both ␤-synuclein/PNP14 (24, 35) and ␥-synuclein/BCSG1/persyn (7, 26, 29) have a very high degree of amino acid similarity with ␣-synuclein within the N-terminal KTK repeat region of the protein molecule, and this is reflected in such common features of synucleins as a native unfolded state in physiological solutions, reversible binding to lipid vesicles, and localization in presynaptic terminals (13,25,31). However, the C-terminal regions of synucleins, although all highly acidic, are rather different (7, 29, 52). It is perhaps this structural diversity that leads to differences in the behavior of synucleins in vitro and in various in vivo model systems. Consistent with the finding that ␤-synuclein and ␥-synuclein are much less fibrillogenic than ␣-synuclein (4, 47, 55), aggregates of these two proteins are not constituents of Lewy b...

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Genomic Structure and Chromosomal Localization of the Mouse Persyn Gene

Cited by 4 publications

References 16 publications

α-Synuclein Promotes Mitochondrial Deficit and Oxidative Stress

α-Synuclein Promotes Mitochondrial Deficit and Oxidative Stress

Synucleins and their relationship to Parkinson’s disease

Neurons Expressing the Highest Levels of γ-Synuclein Are Unaffected by Targeted Inactivation of the Gene

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