TY  - JOUR
A1  - Sian-Hulsmann, Jeswinder
A1  - Riederer, Peter
T1  - The nigral coup in Parkinson's Disease by α-synuclein and its associated rebels
JF  - Cells
N2  - The risk of Parkinson's disease increases with age. However, the etiology of the illness remains obscure. It appears highly likely that the neurodegenerative processes involve an array of elements that influence each other. In addition, genetic, endogenous, or exogenous toxins need to be considered as viable partners to the cellular degeneration. There is compelling evidence that indicate the key involvement of modified α-synuclein (Lewy bodies) at the very core of the pathogenesis of the disease. The accumulation of misfolded α-synuclein may be a consequence of some genetic defect or/and a failure of the protein clearance system. Importantly, α-synuclein pathology appears to be a common denominator for many cellular deleterious events such as oxidative stress, mitochondrial dysfunction, dopamine synaptic dysregulation, iron dyshomeostasis, and neuroinflammation. These factors probably employ a common apoptotic/or autophagic route in the final stages to execute cell death. The misfolded α-synuclein inclusions skillfully trigger or navigate these processes and thus amplify the dopamine neuron fatalities. Although the process of neuroinflammation may represent a secondary event, nevertheless, it executes a fundamental role in neurodegeneration. Some viral infections produce parkinsonism and exhibit similar characteristic neuropathological changes such as a modest brain dopamine deficit and α-synuclein pathology. Thus, viral infections may heighten the risk of developing PD. Alternatively, α-synuclein pathology may induce a dysfunctional immune system. Thus, sporadic Parkinson's disease is caused by multifactorial trigger factors and metabolic disturbances, which need to be considered for the development of potential drugs in the disorder.
KW  - Parkinson's disease
KW  - substantia nigra
KW  - alpha-synuclein
KW  - genetics
KW  - iron
KW  - neuroinflammation
KW  - viruses
KW  - immunology
KW  - aging and cell death
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234073
SN  - 2073-4409
VL  - 10
IS  - 3
ER  - 
TY  - JOUR
A1  - Plum, Sarah
A1  - Eggers, Britta
A1  - Helling, Stefan
A1  - Stepath, Markus
A1  - Theiss, Carsten
A1  - Leite, Renata E. P.
A1  - Molina, Mariana
A1  - Grinberg, Lea T.
A1  - Riederer, Peter
A1  - Gerlach, Manfred
A1  - May, Caroline
A1  - Marcus, Katrin
T1  - Proteomic characterization of synaptosomes from human substantia nigra indicates altered mitochondrial translation in Parkinson's disease
JF  - Cells
N2  - The pathological hallmark of Parkinson's disease (PD) is the loss of neuromelanin-containing dopaminergic neurons within the substantia nigra pars compacta (SNpc). Additionally, numerous studies indicate an altered synaptic function during disease progression. To gain new insights into the molecular processes underlying the alteration of synaptic function in PD, a proteomic study was performed. Therefore, synaptosomes were isolated by density gradient centrifugation from SNpc tissue of individuals at advanced PD stages (N = 5) as well as control subjects free of pathology (N = 5) followed by mass spectrometry-based analysis. In total, 362 proteins were identified and assigned to the synaptosomal core proteome. This core proteome comprised all proteins expressed within the synapses without regard to data analysis software, gender, age, or disease. The differential analysis between control subjects and PD cases revealed that CD9 antigen was overrepresented and fourteen proteins, among them Thymidine kinase 2 (TK2), mitochondrial, 39S ribosomal protein L37, neurolysin, and Methionine-tRNA ligase (MARS2) were underrepresented in PD suggesting an alteration in mitochondrial translation within synaptosomes.
KW  - synaptosomes
KW  - proteomics
KW  - Parkinson's disease
KW  - substantia nigra pars compacta
KW  - mitochondrial pathology
KW  - mitochondrial translation
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219978
SN  - 2073-4409
VL  - 9
IS  - 12
ER  -