Does 22q11.2 deletion syndrome contribute to the genetic aetiology of Parkinson’s disease?

Journal of Neurology -     

What is the role of the cerebellum in the pathophysiology of dystonia?

Journal of Neurology -     

HSPGs glypican-1 and glypican-4 are human neuronal proteins characteristic of different neural phenotypes

Generating neurons from human stem cells has potential for brain damage therapy and neurogenesis modeling, but current efficacy is limited by culture heterogeneity and the lack of markers. We have previously reported the heparan sulfate proteoglycans (HSPGs) glypican-1 (GPC1) and -4 (GPC4) as the markers of lineage-specific human neural stem cells (hNSCs) and mediators of hNSC lineage potential. Here, we further examined phenotypical characteristics and GPC1 and GPC4 during neural differentiation of hNSCs in the presence of two neurogenic growth factors reported to bind to heparan sulfate: brain-derived neurotrophic factor (BDNF) and platelet-derived growth factor-B (PDGF-B). In hNSC neural cultures, GPC1 and GPC4 were expressed along neurites and cell bodies in long-term (40–60 days) neural differentiation cultures demonstrating the areas of differential localization—suggesting potentially different functions. Neural differentiation cultures in the presence of BDNF or PDGF-B generated phenotypically different neural cells with BDNF treatment associated with higher GPC4 versus GPC1 expression, increased heterogeneity, and differential neuron subtype marker expression to PDGF-B cultures. PDGF-B cultures exhibited higher levels of spontaneous activity and reduced heterogeneity over long-term culture associated with decreased GPC4. Untreated neural cultures were highly variable, supporting the use of neuroregulatory growth factors for guided differentiation. Targeted siRNA downregulation of GPC1/4 reduced neural differentiation markers and altered response to exogenous BDNF and PDGF-B. This work confirms GPC1 and GPC4 as regulators of human neural differentiation and supports their use as novel markers of neural cell characterization.     

Use of remote monitoring and integrated platform for the evaluation of sleep quality in adult-onset idiopathic cervical dystonia

Journal of Neurology - Up to 70% of individuals diagnosed with adult-onset idiopathic focal cervical dystonia (AOIFCD) report difficulties with sleep. Larger cohort studies using wrist-worn...     

Repurposed drugs for use in Parkinson’s disease

Journal of Neurology -