The genetic background of Parkinson's disease: current progress and future prospects

Kalinderi, Kallirhoe; Bostantjopoulou, Sevasti; Fidani, Liana

doi:10.1111/ane.12563

Cited by 219 publications

(164 citation statements)

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“…Beside environmental factors, several causative or susceptibility genes have been identified in PD, many of them having direct implications in mitochondrial dysfunction (Kalinderi et al, 2016). Peroxisome proliferator-activated receptor-gamma (PPARγ) coactivator-1 alpha (PGC-1α) is one of them, which may play a role in PD pathogenesis as well.…”

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confidence: 99%

Effect of MPTP on mRNA expression of PGC-1α in mouse brain

et al. 2017

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The peroxisome proliferator-activated receptor-γ (PPARγ) coactivator 1α (PGC-1α) is a key regulator of mitochondrial biogenesis, respiration and adaptive thermogenesis. Beside the full-length protein (FL-PGC-1α), several other functionally active PGC-1α isoforms were identified as a result of alternative splicing (e.g., N-truncated PGC-1α; NT-PGC-1α) or alternative promoter usage (e.g., central nervous system-specific PGC-1α isoforms; CNS-PGC-1α). The achievement of neuroprotection via the CNS-targeted pharmacological stimulation is limited due to the poor penetration of the blood brain barrier (BBB) by the proposed pharmaceutical agents, so preconditioning emerged as another option. The current study aimed at the examination of how the expression levels of FL-, NT-, CNS-and reference PGC-1α isoforms change in different brain regions following various 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment regimens, including the chronic low dose treatment for preconditioning. Ninety minutes following the acute treatment regimen, the expression level of FL-, NT-and CNS-PGC-1α isoforms increased significantly in the striatum, cortex and cerebellum. However, this elevation was diminished 7 days following the last MPTP injection in this acute treatment regimen. The chronic low dose administration of MPTP, which did not cause significant toxic effect in light of the relatively unaltered dopamine levels, neither resulted in any significant change of PGC-1α expression as well. The elevation of PGC-1α levels following acute treatment may demonstrate a short-term compensatory mechanism against the mitochondrial damage induced by the complex I inhibitor MPTP. However, drug-induced preconditioning by chronic low dose MPTP seems not to induce protective responses via the PGC-1α system.

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confidence: 99%

Effect of MPTP on mRNA expression of PGC-1α in mouse brain

et al. 2017

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“…The parkinsonian symptoms are associated with various gene mutations such as Parkin and SNCA Kalinderi et al 2016; in this case, missense mutated SNCA-encoded α-synuclein protein causes Lewy body-like pathology, which can also be identified in postgrafted nigral cells 14 years after transplantation Kordower et al 2008. Therefore, PD patients with missense mutated SNCA i.e., Ala53Thr, Glu46Lys, His50Gln, Gly51Asp, and Ala30Pro are selected as donors of adult human dermal fibroblasts (HDF) for hiPSC generation Kim et al 2014.…”

Section: Selection Criteria For Pd Patientsmentioning

confidence: 99%

Transmission Mechanism of Lewy Body-Like α-Synucleinopathies in Dopaminergic Neurons Derived from Human Induced Pluripotent Stem Cells

Lin¹

2018

RIO

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Grafting of cells in Parkinson's disease (PD) results in a prion-like infection, exhibiting a Lewy body-like pathology, caused by the recipient cells. The transmission mechanism of Lewy bodies is not completely understood. Therefore, a research idea with a novel experimental strategy is proposed to investigate the transmission mechanism of α-synuclein pathology using PD patient-derived human induced pluripotent stem cells (hiPSC) in an in vitro human cellular and molecular PD model and in vivo mouse PD model for dopaminergic neuron transplantation.

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“…The exact etiology remains unclear but a common thread of thought it that there are combined causal roots of genetics and environment. Approximately 5-10% cases are known to be due to genetic causes (monogenic form) in PD [33,34]. Environmental risks are from a number of sources that include most commonly pesticide exposure, living in rural settings, well water consumption, herbicide exposure and living in proximity to industrial plants or quarries.…”

Section: Problem Statementmentioning

confidence: 99%