Generation of isogenic control DJ-1-delP GC13 for the genetic Parkinson's disease-patient derived iPSC line DJ-1-delP (LCSBi008-A-1).

We describe the generation of an isogenic control cell line DJ-1-delP GC13 from an induced pluripotent stem cell (iPSC) line DJ-1-delP LCSBi008-A that was derived from fibroblasts obtained from a Parkinson's disease (PD) patient. Using CRISPR/Cas9 technology, we corrected the disease causing c.471_473delGCC homozygous mutation in the PARK7 gene leading to p.

Mitochondria interaction networks show altered topological patterns in Parkinson's disease.

Mitochondrial dysfunction is linked to pathogenesis of Parkinson's disease (PD). However, individual mitochondria-based analyses do not show a uniform feature in PD patients. Since mitochondria interact with each other, we hypothesize that PD-related features might exist in topological patterns of mitochondria interaction networks (MINs).

Mitochondrial and Clearance Impairment in p.D620N VPS35 Patient-Derived Neurons.

Background: VPS35 is part of the retromer complex and is responsible for the trafficking and recycling of proteins implicated in autophagy and lysosomal degradation, but also takes part in the degradation of mitochondrial proteins via mitochondria-derived vesicles. The p.D620N mutation of VPS35 causes an autosomal-dominant form of Parkinson's disease (PD), clinically representing typical PD.

Bidirectional Relation Between Parkinson's Disease and Glioblastoma Multiforme.

Cancer and Parkinson's disease (PD) define two disease entities that include opposite concepts. Indeed, the involved mechanisms are at different ends of a spectrum related to cell survival - one due to enhanced cellular proliferation and the other due to premature cell death. There is increasing evidence indicating that patients with neurodegenerative diseases like PD have a reduced incidence for most cancers.

A patient-based model of RNA mis-splicing uncovers treatment targets in Parkinson's disease.

Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder with monogenic forms representing prototypes of the underlying molecular pathology and reproducing to variable degrees the sporadic forms of the disease. Using a patient-based in vitro model of -linked PD, we identified a U1-dependent splicing defect causing a drastic reduction in DJ-1 protein and, consequently, mitochondrial dysfunction. Targeting defective exon skipping with genetically engineered U1-snRNA recovered DJ-1 protein expression in neuronal precursor cells and differentiated neurons.

Induced pluripotent stem cell line (LCSBi001-A) derived from a patient with Parkinson's disease carrying the p.D620N mutation in VPS35.

Fibroblasts were obtained from a 76 year-old man diagnosed with Parkinson's disease (PD). The disease is caused by a heterozygous p.D620N mutation in VPS35.

Quality Control Strategy for CRISPR-Cas9-Based Gene Editing Complicated by a Pseudogene.

CRISPR-Cas9 mediated gene editing in induced pluripotent stem cells became an efficient tool to investigate biological mechanisms underlying genetic-driven diseases while accounting for the respective genetic background. This technique relies on the targeting of a specific nucleotide sequence present in the gene of interest. Therefore, the gene editing of some genes can be complicated by non-coding pseudogenes presenting a high homology of sequence with their respective genes.

Plasma Amyloid Is Associated with White Matter and Subcortical Alterations and Is Modulated by Age and Seasonal Rhythms in Mouse Lemur Primates.

Accumulation of amyloid-β (Aβ) peptides in the brain is a critical early event in the pathogenesis of Alzheimer's disease (AD), the most common age-related neurodegenerative disorder. There is increasing interest in measuring levels of plasma Aβ since this could help in diagnosis of brain pathology. However, the value of plasma Aβ in such a diagnosis is still controversial and factors modulating its levels are still poorly understood.