Huntington's disease: changes in saccades and hand-tapping over 3 years.

Saccades and hand-tapping are both potential biomarkers in patients with Huntington's disease (HD). While it is well known that patients with manifest Huntington's disease display abnormalities in both of these tasks, less is known about how these abnormalities progress over time, or to what extent premanifest patients are affected. This study was designed to address these issues.

The relation between anger and different forms of disgust: implications for emotion recognition impairments in Huntington's disease.

Initial reports of emotion recognition in Huntington's disease (HD) found disproportionate impairments in recognising disgust. Not all subsequent studies have found this pattern, and a review of the literature to date shows that marked impairments in recognising anger are also often seen in HD. However, the majority of studies have based their conclusions on a single test of facial expression recognition.

Association of the human leucocyte antigen region with susceptibility to Parkinson's disease.

Objective: The core pathology of Parkinson's disease (PD) is a loss of the dopaminergic neurons in the nigro-striatal pathway, but this is only part of a more widespread pathological process, the nature of which is unknown. Recent data suggest a possible role for inflammation in this disease process. The Human Leucocyte Antigen (HLA) region is one of the most important genetic susceptibility factors in many immune-mediated diseases but has not been extensively investigated in PD.

Parkinson's disease and 2009: recent advances.

This short review summarises the PD related research published in the Journal of Neurology in 2009.

Astrocyte-produced ephrins inhibit schwann cell migration via VAV2 signaling.

Schwann cells are a promising candidate for bridging spinal cord injuries and remyelinating axons. However, grafted Schwann cells show little intermingling with host astrocytes and therefore limited migration from transplant sites. This leads to the formation of a sharp border between host astrocytes and Schwann cells, which results in axons stalling at the graft-host interface and failing to exit the graft.

How vital is sleep in Huntington's disease?

Huntington's disease (HD) is a fatal neurodegenerative disease caused by an abnormal expansion of a CAG repeat in exon 1 of the HD gene on chromosome 4. The disease runs a debilitating and progressive course with an average survival of 15-25 years after disease onset. HD patients classically develop involuntary movements including chorea, as well as progressive cognitive and psychiatric disturbances, although a number of other features have also been reported, including changes in sleep and circadian rhythms; it is this latter area that forms the focus of this review.

Abnormal tau phosphorylation in primary progressive multiple sclerosis.

Although neurodegeneration is the pathological substrate of progression in multiple sclerosis (MS), the underlying mechanisms remain unresolved. Abnormal phosphorylation of tau, implicated in the aetiopathogenesis of a number of classic neurodegenerative disorders, has also recently been described in secondary progressive MS (SPMS). In contrast to SPMS, primary progressive MS (PPMS) represents a significant subset of patients with accumulating neurological disability from onset.

Adult neurogenesis is unaffected by a functional knock-out of MHC class I in mice.

The major histocompatibility complex (MHC) class I has a role in the regulation of immune responses and has been implicated recently in neural plasticity and neurogenesis. We therefore sought to investigate in functional MHC class I knockout mice, transporter associated with antigen processing 1 (TAP1) KO, whether there are alterations in adult neurogenesis. We found no significant differences in cell proliferation or neurogenesis in either the dentate gyrus or subventricular zone, in TAP1 KO versus wild-type mice at several different time points.

Parkinson's disease and growth factors - are they the answer?

The core loss of dopaminergic neurons in the substantia nigra in Parkinson's disease (PD) coupled to the therapeutic benefits of dopaminergic therapies in patients, simplifies the treatment strategy for this disease. In the context of neurotrophic factors, this distils down to the simple question as to whether a factor exists for these cells that can promote their survival in the face of the degenerative disease process. If such a factor exists, and GDNF seems a strong candidate, then one could anticipate that this treatment would be as effective as L-dopa therapy.

Cognitive follow up of a small cohort of Huntington's disease patients over a 5 year period.

A small group of patients with manifest Huntington's disease (HD) were followed longitudinally to assess cognitive decline in relation to time from disease diagnosis. This article looks at performance on a range of computerised and pencil and paper cognitive tasks in patients 5 years post diagnosis, who were assessed annually for a 5 year follow up period. The almost universal cognitive decline reported in other longitudinal studies of HD was not replicated in this study.

Biomarkers in Huntington's and Parkinson's Disease.

Parkinson's (PD) and Huntington's disease (HD) are chronic neurodegenerative conditions of the brain with a variety of clinical presentations including a disorder of movement and a range of nonmotor deficits. HD is genetic in origin and the causative gene and protein known, namely mutant Huntingtin, which leads to widespread early neuronal dysfunction and death throughout the brain. In contrast, the etiology of sporadic PD is unknown, and the pathology targets the nigrostriatal dopaminergic neurons with the formation of alpha-synuclein positive Lewy bodies.

Using stem cells to mend the retina in ocular disease.

Retinal degenerative diseases are the leading cause of incurable blindness worldwide. Furthermore, existing pharmacological and surgical interventions are only partially effective in halting disease progression, thus adjunctive neuroprotective strategies are desperately needed to preserve vision. Stem cells appear to possess inherent neuroprotective abilities, at least in part by providing neurotrophic support to injured neurons.

The distinct cognitive syndromes of Parkinson's disease: 5 year follow-up of the CamPaIGN cohort.

Cognitive abnormalities are common in Parkinson's disease, with important social and economic implications. Factors influencing their evolution remain unclear but are crucial to the development of targeted therapeutic strategies. We have investigated the development of cognitive impairment and dementia in Parkinson's disease using a longitudinal approach in a population-representative incident cohort (CamPaIGN study, n = 126) and here present the 5-year follow-up data from this study.

Activin/Nodal inhibition alone accelerates highly efficient neural conversion from human embryonic stem cells and imposes a caudal positional identity.

Background: Neural conversion from human embryonic stem cells (hESCs) has been demonstrated in a variety of systems including chemically defined suspension culture, not requiring extrinsic signals, as well as in an adherent culture method that involves dual SMAD inhibition using Noggin and SB431542 (an inhibitor of activin/nodal signaling). Previous studies have also determined a role for activin/nodal signaling in development of the neural plate and anterior fate specification. We therefore sought to investigate the independent influence of SB431542 both on neural commitment of hESCs and positional identity of derived neural progenitors in chemically defined substrate-free conditions.

Remyelination - An effective means of neuroprotection.

Remyelination following central nervous system (CNS) demyelination restores rapid saltatory conduction of action potentials and contributes to the maintenance of axonal integrity. This robust regenerative phenomenon stands in contrast to the limited repair capacity that is characteristic of CNS neuronal injury. However, despite its efficiency in experimental models and some clinical diseases, remyelination failure becomes an increasingly pronounced feature of the pathology of chronic multiple sclerosis (MS) lesions.

The role of local protein synthesis and degradation in axon regeneration.

In axotomised regenerating axons, the first step toward successful regeneration is the formation of a growth cone. This requires a variety of dynamic morphological and biochemical changes in the axon, including the appearance of many new cytoskeletal, cell surface and signalling molecules. These changes suggest the activation of coordinated complex cellular processes.

Astrocytes and oligodendrocytes can be generated from NG2+ progenitors after acute brain injury: intracellular localization of oligodendrocyte transcription factor 2 is associated with their fate choice.

Brain injury induces gliosis and scar formation; its principal cell types are mainly astrocytes and some oligodendrocytes. The origin of the astrocytes and oligodendrocytes in the scar remains unclear together with the underlying mechanism of their fate choice. We examined the response of oligodendrocyte transcription factor (Olig)2(+) glial progenitors to acute brain injury.

Emerging drug therapies in Huntington's disease.

Huntington's disease (HD) is a relentless neurodegenerative disease that results in profound disability through a triad of motor, cognitive and neuropsychiatric symptoms. At present, there are very few therapeutic interventions available with the exception of a limited number of drugs that offer mild symptomatic relief. Although the genetic basis of the disease has been identified, the mechanisms behind the cellular pathogenesis are still not clear and as a result no candidate drugs with the potential for disease modification have been found clinically until now.

Dopamine-induced proliferation of adult neural precursor cells in the mammalian subventricular zone is mediated through EGF.

A reduction in dopaminergic innervation of the subventricular zone (SVZ) is responsible for the impaired proliferation of its resident precursor cells in this region in Parkinson's disease (PD). Here, we show that this effect involves EGF, but not FGF2. In particular, we demonstrate that dopamine increases the proliferation of SVZ-derived cells by releasing EGF in a PKC-dependent manner in vitro and that activation of the EGF receptor (EGFR) is required for this effect.

Alpha9 integrin promotes neurite outgrowth on tenascin-C and enhances sensory axon regeneration.

Damaged CNS axons are prevented from regenerating by an environment containing many inhibitory factors. They also lack an integrin that interacts with tenascin-C, the main extracellular matrix glycoprotein of the CNS, which is upregulated after injury. The alpha9beta1 integrin heterodimer is a receptor for the nonalternatively spliced region of tenascin-C, but the alpha9 subunit is absent in adult neurons.

Animal models of neurodegenerative diseases.

Animal models of neurodegenerative disease are excellent tools for studying pathogenesis and therapies including cellular transplantation. In this chapter, we describe different models of Huntington's disease and Parkinson's disease, stereotactic surgery (used in creation of lesion models and transplantation) and finally transplantation studies in these models.

Tau inclusions in retinal ganglion cells of human P301S tau transgenic mice: effects on axonal viability.

Tau inclusions play a key role in the pathogenesis of tauopathies. Altered tau levels have been detected in retina and optic nerve of patients with glaucoma, suggesting the possibility of shared pathogenic mechanisms with tauopathies. Here we report that hyperphosphorylated transgenic tau accumulates in the nerve fibre layer and, from 2 months of age, aggregates into filamentous inclusions in retinal ganglion cells of human P301S tau transgenic mice.

Apolipoprotein E genotype as a risk factor for susceptibility to and dementia in Parkinson's disease.

Further to the well-established association between apolipoprotein E (APOE) and Alzheimer's disease, this gene has also been implicated in both susceptibility to, and dementia in, Parkinson's disease (PD). However studies to date have produced contradictory findings. We conducted a case-control study in a population of 528 PD patients and 512 healthy controls and found no significant difference in allele or genotype distribution of APOE between the two groups.

Evidence for abnormal tau phosphorylation in early aggressive multiple sclerosis.

Although progression in multiple sclerosis is pathologically dominated by neurodegeneration, the underlying mechanism is unknown. Abnormal hyperphosphorylation of tau is implicated in the aetiopathogenesis of some common neurodegenerative disorders. We recently demonstrated the association of insoluble tau with established secondary progressive MS, raising the hypothesis that its accumulation is relevant to disease progression.

An efficient method for derivation and propagation of glioblastoma cell lines that conserves the molecular profile of their original tumours.

A growing body of evidence suggests that glioma stem-like cells are more representative of their parent tumours when cultured under defined serum-free conditions with the mitogens epidermal growth factor (EGF) and fibroblast growth factor (FGF). However, culturing these cells as free-floating spheroids can result in difficulty in efficiently deriving and propagating cell lines. We have combined neurosphere and monolayer culture techniques to improve the efficiency with which cells can be derived from clinical tumour samples under defined serum-free conditions.