Genetic and pharmacologic p32-inhibition rescue CHCHD2-linked Parkinson's disease phenotypes in vivo and in cell models.

Background: Mutations in CHCHD2 have been linked to Parkinson's disease, however, their exact pathophysiologic roles are unclear. The p32 protein has been suggested to interact with CHCHD2, however, the physiological functions of such interaction in the context of PD have not been clarified.

Methods: Interaction between CHCHD2 and p32 was confirmed by co-immunoprecipitation experiments.

Current Opinions and Consensus for Studying Tremor in Animal Models.

Tremor is the most common movement disorder; however, we are just beginning to understand the brain circuitry that generates tremor. Various neuroimaging, neuropathological, and physiological studies in human tremor disorders have been performed to further our knowledge of tremor. But, the causal relationship between these observations and tremor is usually difficult to establish and detailed mechanisms are not sufficiently studied.

Varied pathological and therapeutic response effects associated with CHCHD2 mutant and risk variants.

Mutations and polymorphic risk variant of coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) have been associated with late-onset Parkinson disease. In vivo pathological evidence of CHCHD2 mutations is currently lacking. Utilizing transgenic Drosophila model, we examined the relative pathophysiologic effect of the pathogenic (c.

Derivation of human induced pluripotent stem cell (iPSC) line with LRRK2 gene R1398H variant in Parkinson's disease.

Peripheral blood mononuclear cells (PBMCs) were collected from a clinically diagnosed 72-year old female Parkinson's disease (PD) patient with R1398H variant in the LRRK2 gene. The PMBCs were reprogrammed with the human OSKM transcription factors using the Sendai-virus reprogramming system. The transgene-free iPSC showed pluripotency confirmed by immunofluorescent staining for pluripotency markers and differentiated into the 3 germ layers in vivo.

FUS-linked essential tremor associated with motor dysfunction in Drosophila.

Essential tremor (ET) is one of the most common adult-onset neurological disorders which produce motor and non-motor symptoms. To date, there are no gold standard pathological hallmarks of ET, and despite a strong genetic contribution toward ET development, only a few pathogenic mutations have been identified. Recently, a pathogenic FUS-Q290X mutation has been reported in a large ET-affected family; however, the pathophysiologic mechanism underlying FUS-linked ET is unknown.

Genetics of essential tremor.

Essential tremor is one of the most common adult-onset movement disorders. While it is recognized that genes play a major role in ET with ≥50% of the affected individuals having a positive family history, identifying underlying genes in both monogenic and complex forms of ET has been a challenging task. Recent discoveries linking LINGO1, FUS and TENM4 to essential tremor have been met with cautious optimism since reproducibility and pathogenicity have been contentious in previously implicated genes.

Association Analysis of COQ2 Variant in Dementia and Essential Tremor.

Objective. COQ2 mutations have been reported in Japanese multiple system atrophy (MSA) patients. We examined the role of COQ2 in patients with dementia and essential tremor (ET), two common neurodegenerative conditions.

In vivo evidence of pathogenicity of VPS35 mutations in the Drosophila.

Mutations of VPS35, a component of the retromer complex have been associated with late onset familial Parkinson's disease. The D620N mutation in VPS35 appears to be most prevalent, however, P316S was found in two cases within the same family and a control, whereas L774M was identified in 6 cases and 1 control. In vivo evidence of their pathogenicity is lacking.

Asymmetric cell division and Notch signaling specify dopaminergic neurons in Drosophila.

In Drosophila, dopaminergic (DA) neurons can be found from mid embryonic stages of development till adulthood. Despite their functional involvement in learning and memory, not much is known about the developmental as well as molecular mechanisms involved in the events of DA neuronal specification, differentiation and maturation. In this report we demonstrate that most larval DA neurons are generated during embryonic development.

Roles of db-cAMP, IBMX and RA in aspects of neural differentiation of cord blood derived mesenchymal-like stem cells.

Mesenchymal stem cells (MSCs) have multilineage differentiation potential which includes cell lineages of the central nervous system; hence MSCs might be useful in the treatment of neurodegenerative diseases such as Parkinson's disease. Although mesenchymal stem cells have been shown to differentiate into the neural lineage, there is still little knowledge about the underlying mechanisms of differentiation particularly towards specialized neurons such as dopaminergic neurons. Here, we show that MSCs derived from human umbilical cord blood (MSC(hUCBs)) are capable of expressing tyrosine hydroxylase (TH) and Nurr1, markers typically associated with DA neurons.

On the roles of Notch, Delta, kuzbanian, and inscuteable during the development of Drosophila embryonic neuroblast lineages.

The generation of cellular diversity in the nervous system involves the mechanism of asymmetric cell division. Besides an array of molecules, including the Par protein cassette, a heterotrimeric G protein signalling complex, Inscuteable plays a major role in controlling asymmetric cell division, which ultimately leads to differential activation of the Notch signalling pathway and correct specification of the two daughter cells. In this context, Notch is required to be active in one sibling and inactive in the other.

Functions of the segment polarity genes midline and H15 in Drosophila melanogaster neurogenesis.

The Drosophila melanogaster ventral nerve cord derives from neural progenitor cells called neuroblasts. Individual neuroblasts have unique gene expression profiles and give rise to distinct clones of neurons and glia. The specification of neuroblast identity provides a cell intrinsic mechanism which ultimately results in the generation of progeny which are different from each other.

Drosophila T box proteins break the symmetry of hedgehog-dependent activation of wingless.

Background: Segmentation of the Drosophila embryo is a classic paradigm for pattern formation during development. The Wnt-1 homolog Wingless (Wg) is a key player in the establishment of a segmentally reiterated pattern of cell type specification. The intrasegmental polarity of this pattern depends on the precise positioning of the Wg signaling source anterior to the Engrailed (En)/Hedgehog (Hh) domain.