Robert J Harvey

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Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of dopaminergic neurons in the substantia nigra. We previously mapped a locus for a rare familial form of PD to chromosome 1p36 (PARK6). Here we show that mutations in PINK1 (PTEN-induced kinase 1) are associated with PARK6. We have identified two homozygous mutations(More)
In mice, targeted deletion of the serine protease HtrA2 (also known as Omi) causes mitochondrial dysfunction leading to a neurodegenerative disorder with parkinsonian features. In humans, point mutations in HtrA2 are a susceptibility factor for Parkinson's disease (PARK13 locus). Mutations in PINK1, a putative mitochondrial protein kinase, are associated(More)
In the mammalian CNS, each neuron typically receives thousands of synaptic inputs from diverse classes of neurons. Synaptic transmission to the postsynaptic neuron relies on localized and transmitter-specific differentiation of the plasma membrane with postsynaptic receptor, scaffolding, and adhesion proteins accumulating in precise apposition to(More)
OBJECTIVE To evaluate the rate of brain atrophy calculated from serial magnetic resonance imaging (MRI) registration as a surrogate marker of disease progression for use in clinical trials in Alzheimer disease (AD). METHODS Eighteen patients with mild to moderate AD and 18 age-matched normal controls underwent 2 MRI brain scans separated by a 12-month(More)
Gephyrin is a multifunctional protein responsible for molybdenum cofactor synthesis and the clustering of glycine and GABA(A) receptors at inhibitory synapses. Based on the structure of its two conserved domains, G and E, gephyrin is thought to form a hexagonal lattice serving as a scaffold for accessory proteins at postsynaptic sites. However, important(More)
The widespread use of elite sires by means of artificial insemination in livestock breeding leads to the frequent emergence of recessive genetic defects, which cause significant economic and animal welfare concerns. Here we show that the availability of genome-wide, high-density SNP panels, combined with the typical structure of livestock populations,(More)
Zinc ions are concentrated in the central nervous system and regulate GABAA receptors, which are pivotal mediators of inhibitory synaptic neurotransmission. Zinc ions inhibit GABAA receptor function by an allosteric mechanism that is critically dependent on the receptor subunit composition: αβ subunit combinations show the highest sensitivity, and αβγ(More)
Prostaglandin E2 (PGE2) is a crucial mediator of inflammatory pain sensitization. Here, we demonstrate that inhibition of a specific glycine receptor subtype (GlyR alpha3) by PGE2-induced receptor phosphorylation underlies central inflammatory pain sensitization. We show that GlyR alpha3 is distinctly expressed in superficial layers of the spinal cord(More)
Mutations in the LRRK2 gene, coding for dardarin, cause dominantly inherited Parkinson's disease (PD). Dardarin is a large protein, and mutations are found throughout the gene including the kinase domain. However, it is not clear if kinase activity is important for the damaging effects of pathogenic mutations. In this study, we noted two cellular phenotypes(More)
OBJECTIVES To determine the prevalence of dementia in people under the age of 65 in a large catchment area, and use these figures to estimate the number of younger people affected by dementia in the UK. DESIGN Epidemiological catchment area prevalence survey. SETTING The London boroughs of Kensington and Chelsea, Westminster, and Hillingdon with a total(More)