Impaired Sonic Hedgehog Responsiveness of Induced Pluripotent Stem Cell-Derived Floor Plate Cells Carrying the LRRK2-I1371V Mutation Contributes to the Ontogenic Origin of Lower Dopaminergic Neuron Yield.

Lower population of dopaminergic (DA) neurons is known to increase susceptibility to Parkinson's disease (PD), and our earlier study showed a lower yield of DA neurons in Leucine-Rich Repeat Kinase Isoleucine 1371 Valine (LRRK2-I1371V) mutation-carrying PD patient-derived induced Pluripotent Stem Cells (iPSCs). Although the role of Sonic Hedgehog (SHH) in DA neurogenesis of floor plate cells (FPCs) is known, the effect of LRRK2 mutations on SHH responsiveness of FPCs impacting DA neuronal yield has not been studied. We investigated SHH responsiveness of FPCs derived from LRRK2-I1371V PD patient iPSCs with regard to the expression of SHH receptors Patched1 (Ptch1) and Smoothened (Smo), in conjunction with nuclear Gli1 (glioma-associated oncogene 1) expression, intracellular Ca rise, and cytosolic cyclic adenosine monophosphate (cAMP) levels upon SHH induction.

Generation of induced pluripotent stem cells (NIMHi015-A) from a Parkinson's Disease patient harbouring a homozygous Exon 3 deletion in the PRKN gene.

The Parkin (PRKN) gene mutation is prevalent in young-onset Parkinson's disease (PD), typically emerging before age 30, accompanied by early motor symptoms. Induced pluripotent stem cells (iPSCs) were derived from peripheral blood mononuclear cells of a PD patient with an exon 3 deletion in PRKN using Sendai-virus reprogramming. PD diagnosis was confirmed via the Unified Parkinson's Disease Rating Scale (UPDRS).

Dopaminergic Neurons Differentiated from LRRK2 I1371V-Induced Pluripotent Stem Cells Display a Lower Yield, α-Synuclein Pathology, and Functional Impairment.

Being a large multidomain protein, LRRK2 has several confirmed pathological mutant variants for PD, and the incidence of these variants shows ethnicity biases. I1371V, a mutation in the GTPase domain, has been reported in East-Asian populations, but there are no studies reported on dopaminergic (DA) neurons differentiated from this variant. The aim here was to assess the yield, function, and α-synuclein pathology of DA neurons differentiated from LRRK2 I1371V iPSCs.

Generation of induced pluripotent stem cells (NIMHi004-A, NIMHi005-A and NIMHi006-A) from healthy individuals of Indian ethnicity with no mutation for Parkinson's disease related genes.

This study describes the generation and characterization of 3 induced pluripotent stem cell lines (iPSCs) generated by somatic reprogramming of peripheral blood mononuclear cells (PBMCs) obtained from healthy individuals. The reprogramming was carried out using non-integrating Sendai virus vectors expressing hKOS, hc-myc and hKlf4. The donors did not carry any mutations for a panel of 13 genes associated with occurrence and progression of Parkinson's disease (PD).

Generation of induced pluripotent stem cells (NIMHi002-A and NIMHi003-A) from two sporadic Parkinson's disease patient of East Indian ethnicity.

Epidemiological studies suggest that about 95% of PD have a sporadic component. We have generated induced pluripotent stem cells (iPSCs) using Sendai-virus reprogramming-method from peripheral blood mononuclear cells of two sporadic PD-patient of East-Indian ethnicity carrying no PD-related gene mutations. PD diagnosis was performed using Unified Parkinson's Disease rating scale (UPDRS) score and confirmed by [F]fluoro-L-dopa [F-DOPA] positron emission tomography (F-DOPA PET).

Generation of induced pluripotent stem cells (NIMHi001-A) from a Parkinson's disease patient of East Indian ethnicity carrying LRRK2 I1371V variant.

Mutations in the Leucine Repeat Rich Kinase-2 (LRRK2) gene have been reported in familial Parkinson's disease (PD) cases. We have generated induced pluripotent stem cells (iPSCs) using Sendai-virus reprogramming-method from peripheral blood mononuclear cells of PD-patient of East-Indian ethnicity carrying the I1371V mutation in LRRK2 gene. PD diagnosis was performed using Unified Parkinson's Disease rating scale (UPDRS) score and confirmed by [F]fluoro-l-dopa [F-DOPA] positron emission tomography (F-DOPA PET).

Diversity, expression and mRNA targeting abilities of Argonaute-targeting miRNAs among selected vascular plants.

Background: Micro (mi)RNAs are important regulators of plant development. Across plant lineages, Dicer-like 1 (DCL1) proteins process long ds-like structures to produce micro (mi) RNA duplexes in a stepwise manner. These miRNAs are incorporated into Argonaute (AGO) proteins and influence expression of RNAs that have sequence complementarity with miRNAs.

Phytochemical analysis and free radical scavenging activity of medicinal plants Gnidia glauca and Dioscorea bulbifera.

Gnidia glauca and Dioscorea bulbifera are traditional medicinal plants that can be considered as sources of natural antioxidants. Herein we report the phytochemical analysis and free radical scavenging activity of their sequential extracts. Phenolic and flavonoid content were determined.