Metal-catalyzed oxidation of alpha-synuclein: helping to define the relationship between oligomers, protofibrils, and filaments.
AuthorsCole NB, Murphy DD, Lebowitz J, Di Noto L, Levine RL, Nussbaum RL,
JournalJ Biol Chem
PubMed ID15615715
'Oxidative stress is implicated in a number of neuro-degenerative diseases and is associated with the selective loss of dopaminergic neurons of the substantia nigra in Parkinson''s disease. The role of alpha-synuclein as a potential target of intracellular oxidants has been demonstrated by the identification of posttranslational modifications of synuclein within ... More
Mitochondrial metabolism in Parkinson's disease impairs quality control autophagy by hampering microtubule-dependent traffic.
'Abnormal presence of autophagic vacuoles is evident in brains of patients with Parkinson''s disease (PD), in contrast to the rare detection of autophagosomes in a normal brain. However, the actual cause and pathological significance of these observations remain unknown. Here, we demonstrate a role for mitochondrial metabolism in the regulation ... More
Polo-like kinase 2 regulates selective autophagic a-synuclein clearance and suppresses its toxicity in vivo.
AuthorsOueslati A, Schneider BL, Aebischer P, Lashuel HA,
Journal
PubMed ID23983262
'An increase in a-synuclein levels due to gene duplications/triplications or impaired degradation is sufficient to trigger its aggregation and cause familial Parkinson disease (PD). Therefore, lowering a-synuclein levels represents a viable therapeutic strategy for the treatment of PD and related synucleinopathies. Here, we report that Polo-like kinase 2 (PLK2), an ... More
Neurological and neurodegenerative alterations in a transgenic mouse model expressing human alpha-synuclein under oligodendrocyte promoter: implications for multiple system atrophy.
AuthorsShults CW, Rockenstein E, Crews L, Adame A, Mante M, Larrea G, Hashimoto M, Song D, Iwatsubo T, Tsuboi K, Masliah E,
JournalJ Neurosci
PubMed ID16291942
'Multiple system atrophy (MSA) is a progressive, neurodegenerative disease characterized by parkinsonism, ataxia, autonomic dysfunction, and accumulation of alpha-synuclein (alpha-syn) in oligodendrocytes. To better understand the mechanisms of neurodegeneration and the role of alpha-syn accumulation in oligodendrocytes in the pathogenesis of MSA, we generated transgenic mouse lines expressing human (h) ... More
A Drosophila model of Parkinson's disease.
AuthorsFeany MB, Bender WW
JournalNature
PubMed ID10746727
'Parkinson''s disease is a common neurodegenerative syndrome characterized by loss of dopaminergic neurons in the substantia nigra, formation of filamentous intraneuronal inclusions (Lewy bodies) and an extrapyramidal movement disorder. Mutations in the alpha-synuclein gene are linked to familial Parkinson''s disease and alpha-synuclein accumulates in Lewy bodies and Lewy neurites. Here ... More
Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson's disease and dementia with Lewy bodies.
AuthorsBaba M, Nakajo S, Tu PH, Tomita T, Nakaya K, Lee VM, Trojanowski JQ, Iwatsubo T
JournalAm J Pathol
PubMed ID9546347
'Lewy bodies (LBs) are hallmark lesions of degenerating neurons in the brains of patients with Parkinson''s disease (PD) and dementia with Lewy bodies (DLB). Recently, a point mutation in the gene encoding the presynaptic alpha-synuclein protein was identified in some autosomal-dominantly inherited familial PD pedigrees, and light microscopic studies demonstrated ... More
Antibodies to alpha-synuclein detect Lewy bodies in many Down's syndrome brains with Alzheimer's disease.
AuthorsLippa CF, Schmidt ML, Lee VM, Trojanowski JQ
JournalAnn Neurol
PubMed ID10072050
Immunohistochemical examination of 20 Down's syndrome brains, using antibodies to alpha-, beta-, and gamma-synuclein, demonstrated many alpha-synuclein-positive Lewy bodies and dystrophic neurites in 50% of amygdala samples from Down's syndrome brains with Alzheimer's disease. Similar lesions were less common in other regions of these brains, none of which contained beta-synuclein ... More
Fluorescence studies suggest a role for alpha-synuclein in the phosphatidylinositol lipid signaling pathway.
AuthorsNarayanan V, Guo Y, Scarlata S
JournalBiochemistry
PubMed ID15641770
Alpha-synuclein plays a key role in the pathogenesis of many neurodegenerative diseases. To date, its cellular role has yet to be determined, although it has been proposed to be connected to calcium and G protein-mediated dopamine signaling. Alpha-synuclein is known to bind strongly to model membrane surfaces where it may ... More