Disease relevance of SNCB

• We characterized beta-synuclein, the non-amyloidogenic homolog of alpha-synuclein, as an inhibitor of aggregation of alpha-synuclein, a molecule implicated in Parkinson's disease [1].
• Such an anti-amyloidogenic property of beta-synuclein might also provide a novel strategy for the treatment of neurodegenerative disorders [1].
• An antiaggregation gene therapy strategy for Lewy body disease utilizing beta-synuclein lentivirus in a transgenic model [2].
• Of medulloblastomas, 76% have immunoreactivity for either alpha- or beta-synuclein or both; no immunoreactivity for gamma-synuclein is seen in medulloblastomas [3].
• Down-regulation of Akt expression resulted in an increased susceptibility to rotenone toxicity, whereas transfection with a lentiviral vector encoding for beta-synuclein was protective [4].

Psychiatry related information on SNCB

• Beta-synuclein gene alterations in dementia with Lewy bodies [5].

High impact information on SNCB

• beta-Synuclein inhibits alpha-synuclein aggregation: a possible role as an anti-parkinsonian factor [1].
• Similar lesions were less common in other regions of these brains, none of which contained beta-synuclein or gamma-synuclein abnormalities [6].
• These phenotypes were not seen upon expression of beta-synuclein [7].
• Beta-synuclein regulates Akt activity in neuronal cells. A possible mechanism for neuroprotection in Parkinson's disease [4].
• Recent studies have shown that the neurodegenerative process in disorders with Lewy body formation, such as Parkinson's disease and dementia with Lewy bodies, is associated with alpha-synuclein accumulation and that beta-synuclein might protect the central nervous system from the neurotoxic effects of alpha-synuclein [4].

Biological context of SNCB

• This was accompanied by a lower DNA fragmentation as evidenced by the reduction of propidium iodide incorporation measured by fluorescence-activated cell sorter analysis. beta-Synuclein strongly reduces staurosporine-induced caspase 3 activity and immunoreactivity [8].
• Metal ions, oxidative stress, and beta-amyloid 1-42 (Abeta1-42) are important induction factors for alpha-syn aggregation. beta-Synuclein (beta-syn) can counteract alpha-syn aggregation [9].
• Double-transgenic progeny of these mice that also express human beta-synuclein, a homologue of alpha-synuclein, show significant amelioration of all three phenotypes [10].
• This gene is composed of five exons, which encode a 127 amino acid protein that is highly homologous to alpha-synuclein, which is mutated in some Parkinson's disease families, and to beta-synuclein [11].
• Assignment of human alpha-synuclein (SNCA) and beta-synuclein (SNCB) genes to chromosomes 4q21 and 5q35 [12].

Anatomical context of SNCB

• In control cases, highest levels of expression were observed in the neocortex and the lowest in basal ganglia and substantia nigra. beta-Synuclein was the most abundant message (75-80%), followed by gamma-synuclein (10-15%) and alpha-synuclein (8-10%) [13].
• Alpha-synuclein and its homologue beta-synuclein are both natively unfolded proteins that colocalize in presynaptic terminals of neurons in many regions of the brain, including those of dopamine-producing cells of the substantia nigra [14].
• This effect was specific for nigral alpha-synuclein as no age-related changes were found in the ventral tegmental area nor were there changes in the nigra for non-pathogenic beta-synuclein [15].
• The novel expression of beta-synuclein in astrocytes may provide an important insight about the role of this protein [16].
• Furthermore, beta-synuclein immunoreactivity was present in astrocytes, but not in oligodendrocytes, in normal human brain tissues [16].

Associations of SNCB with chemical compounds

• Certain metals (Zn(2+), Pb(2+), and Cu(2+)) induce a partially folded conformation of beta-synuclein that triggers rapid fibrillation [14].
• RESULTS: Two amino acid alterations were identified in unrelated DLB index cases: a valine to methionine substitution at codon 70 (V70M) and a proline to histidine substitution at codon 123 (P123H), both in the beta-synuclein gene [5].
• Beta-synuclein transfection resulted in increased Akt activity and conferred protection from the neurotoxic effects of rotenone [4].
• The Ca(2+)-binding site consists of a novel C-terminally localized acidic 32-amino acid domain also present in the homologue beta-synuclein, as shown by Ca(2+) binding to truncated recombinant and synthetic alpha-synuclein peptides [17].
• The main objective of the present study was to investigate the potential involvement of the serine threonine kinase Akt (also known as protein kinase B) signaling pathway in the mechanisms of beta-synuclein neuroprotection [4].

Regulatory relationships of SNCB

• We establish that beta-synuclein triggers a drastic reduction of p53 expression and transcriptional activity [8].
• Moreover, beta-synuclein inhibited the amyloid formation of both Abeta(1-40) and alpha-synuclein [18].

Other interactions of SNCB

• Our results raise the possibility that beta-synuclein might be a natural negative regulator of alpha-synuclein aggregation and that a similar class of endogenous factors might regulate the aggregation state of other molecules involved in neurodegeneration [1].
• Co-incubating beta-synuclein with gamma-synuclein had no effect on the inhibition of the 20 S proteasome by monomeric gamma-synuclein [19].
• We show that in basal and staurosporine-induced conditions the number of terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling (TUNEL)-positive beta-synuclein-expressing neurons was drastically lower than in mock-transfected TSM1 cells [8].
• We discuss the possibility of a pathogenic role for CNTF and a protective role for beta-synuclein in experimental hyperammonemia [20].
• Heat-induced inactivation of citrate synthase was significantly protected by beta-synuclein [18].

Analytical, diagnostic and therapeutic context of SNCB

• Together, these data further support a role for beta-synuclein in regulating the conformational state of alpha-synuclein and suggest that this gene transfer approach might have potential for the development of alternative therapies for PD and DLB [2].
• Histopathology and immunohistochemistry analysis of index case brain sections revealed widespread Lewy body pathology and alpha-synuclein aggregation without evidence of beta-synuclein aggregation [5].
• We attributed the amelioration of alpha-synuclein neurotoxicity in such bigenic mice to the ability of beta-synuclein to reduce alpha-synuclein protein expression based upon I(125) autoradiography quantification [21].
• Possible implication of ciliary neurotrophic factor (CNTF) and beta-synuclein in the ammonia effect on cultured rat astroglial cells: A study using DNA and protein microarrays [20].
• After protein microarray data filtration by signal intensity, x-fold change and z-score, 11 proteins were selected, among which the significant increase in beta-synuclein was confirmed by Western blot [20].

References