Neuromolecular medicine
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Neuromolecular medicine · Jan 2006
ReviewInherited focal, episodic neuropathies: hereditary neuropathy with liability to pressure palsies and hereditary neuralgic amyotrophy.
Hereditary neuropathy with liability to pressure palsies (HNPP; also called tomaculous neuropathy) is an autosomal-dominant disorder that produces a painless episodic, recurrent, focal demyelinating neuropathy. HNPP generally develops during adolescence, and may cause attacks of numbness, muscular weakness, and atrophy. Peroneal palsies, carpal tunnel syndrome, and other entrapment neuropathies may be frequent manifestations of HNPP. ⋯ In some HNA pedigrees there are characteristic facial features, including hypotelorism. The prognosis for recovery of normal function of affected limbs in HNA is good, although recurrent episodes may cause residual deficits. HNA is genetically linked to chromosome 17q25, where mutations in the septin-9 (SEPT9) gene have been found.
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Neuromolecular medicine · Jan 2003
NF2 tumor suppressor gene: a comprehensive and efficient detection of somatic mutations by denaturing HPLC and microarray-CGH.
The NF2 tumor suppressor gene, located in chromosome 22q12, is involved in the development of multiple tumors of the nervous system, either associated with neurofibromatosis 2 or sporadic ones, mainly schwannomas and meningiomas. In order to evaluate the role of the NF2 gene in sporadic central nervous system (CNS) tumors, we analyzed NF2 mutations in 26 specimens: 14 meningiomas, 4 schwannomas, 4 metastases, and 4 other histopathological types of neoplasms. Denaturing high performance liquid chromatography (denaturing HPLC) and comparative genomic hybridization on a DNA microarray (microarray- CGH) were used as scanning methods for small mutations and gross rearrangements respectively. ⋯ No NF2 mutations were found in other histopathological types of CNS tumors. These results provide additional evidence that mutations in the NF2 gene play an important role in the development of sporadic meningiomas and schwannomas. Denaturing HPLC analysis of small mutations and microarray-CGH of large deletions are complementary, fast, and efficient methods for the detection of mutations in tumor tissues.
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Neuromolecular medicine · Jan 2002
Comparative StudyAdverse effect of a presenilin-1 mutation in microglia results in enhanced nitric oxide and inflammatory cytokine responses to immune challenge in the brain.
Inflammatory processes involving glial cell activation are associated with amyloid plaques and neurofibrillary tangles, the cardinal neuropathological lesions in the brains of Alzheimer's disease (AD) patients, However, it is unclear whether these inflammatory processes occur as a response to neuronal degeneration or might represent more seminal events in the disease process. Some cases of AD are caused by mutations in presenilin-1 (PS1), and it has been shown that PS1 mutations perturb neuronal calcium homeostasis, promote increased production of amyloid beta-peptide (Abeta), and render neurons vulnerable to synaptic dysfunction, excitotoxicity, and apoptosis. Although glial cells express PS1, it is not known if PS1 mutations alter glial cell functions. ⋯ Studies of cultured microglia from PS1 mutant and wild-type mice reveal that PS1 is expressed in microglia and that the PS1 mutation confers a heightened sensitivity to LPS, as indicated by superinduction of inducible nitric oxide synthase (NOS) and activation of mitogen-activated protein kinase (MAPK). These findings demonstrate an adverse effect of PS1 mutations on microglial cells that results in their hyperactivation under pro-inflammatory conditions, which may, together with direct effects of mutant PS1 in neurons, contribute to the neurodegenerative process in AD. These findings also have important implications for development of a "vaccine" for the prevention or treatment of AD.
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Neuromolecular medicine · Jan 2002
ReviewAlpha-synuclein and presynaptic function: implications for Parkinson's disease.
This article focuses on alpha-synuclein's role in normal and pathological axonal and presynaptic functions and its relationship to Parkinson's disease. It is not possible to mention all the contributions to aspects of this area. Readers interested in alpha-synuclein's relation to aggregation, Lewy lesions, and pathological modifications are referred to the many reviews (see Goldberg and Lansbury 2000; Galvin 2001a; Goedert 2001).