Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The protein gene product PGP 9.5 is one of the major polypeptides in neurons. It can act as a ubiquitin carboxyl-terminal hydrolase in ubiquitin-mediated degradation of proteins. The present study was performed to find out if human cases with spinal cord trauma present immunohistochemical signs of PGP 9.5 accumulation in injured axons known to accumulate ubiquitin. For comparison, we used six autopsy cases without spinal cord pathology, one case with syringomyelia, one case with ischaemic injury of the cord, and six ALS cases. Controls presented PGP 9.5-immunostained axons of weak to moderate intensity in the longitudinal tracts. Immunoreactivity was not detected in nerve cell bodies, glial cells or axons of the grey matter. All nine trauma cases showed axonal swellings, but their numbers varied. Intensely immunostained axonal swellings were particularly abundant in cases with a survival period up to 1 month after trauma. Strongly immunoreactive axons were present also in the cases with infarct and syringomyelia. In conclusion, human cases with spinal cord trauma and other focal injuries present signs of PGP 9.5 accumulation in severed axons possibly resulting from disturbed axonal transport. PGP 9.5 thus seems to be present and may take part in ubiquitin-mediated degradation of proteins in injured axons of the spinal cord.
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PMID:Accumulation of immunoreactivity to ubiquitin carboxyl-terminal hydrolase PGP 9.5 in axons of human cases with spinal cord lesions. 989 Feb 71

The receptor tyrosine kinase Ret (c-Ret) transduces the glial cell line-derived neurotrophic factor (GDNF) signal, one of the neurotrophic factors related to the degeneration process or the regeneration activity of motor neurons in amyotrophic lateral sclerosis (ALS). The phosphorylation of several tyrosine residues of c-Ret seems to be altered in ALS. c-Ret is expressed in motor neurons and in the enteric nervous system (ENS) during the embryonic period. The characteristics of the ENS allow using it as model for central nervous system (CNS) study and being potentially useful for the research of human neurological diseases such as ALS. The aim of the present study was to investigate the cellular localization and quantitative evaluation of marker c-Ret in the adult human gut. To assess the nature of c-Ret positive cells, we performed colocalization with specific markers of cells that typically are located in the enteric ganglia. The colocalization of PGP9.5 and c-Ret was preferentially intense in enteric neurons with oval morphology and mostly peripherally localized in the ganglion, so we concluded that the c-Ret receptor is expressed by a specific subtype of enteric neurons in the mature human ENS of the gut. The functional significance of these c-Ret positive neurons is discussed.
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PMID:New insights into c-Ret signalling pathway in the enteric nervous system and its relationship with ALS. 2486 25

Gene and cell-based therapies comprise innovative aspects of regenerative medicine. Even though stem cells represent a highly potential therapeutic strategy, their wide-spread exploitation is marred by ethical concerns, potential for malignant transformation and a plethora of other technical issues, largely restricting their use to experimental studies. Utilizing genetically modified human umbilical cord blood mono-nuclear cells (hUCB-MCs), this communication reports enhanced differentiation of transplants in a mouse model of amyotrophic lateral sclerosis (ALS). Over-expressing Oct4 and Sox2 induced production of neural marker PGP9.5, as well as transformation of hUCB-MCs into micro-glial and endothelial lines in ALS spinal cords. In addition to producing new nerve cells, providing degenerated areas with trophic factors and neo-vascularisation might prevent and even reverse progressive loss of moto-neurons and skeletal muscle paralysis.
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PMID:Over-expression of Oct4 and Sox2 transcription factors enhances differentiation of human umbilical cord blood cells in vivo. 2512 62

Sensory alterations have been described in both amyotrophic lateral sclerosis (ALS) patients and mouse models. While involvement of intraepidermal and subepidermal axons has been shown in skin biopsies of ALS patients, it is unclear if the SOD1(G93A) mouse presents similar alterations. We analyzed the epidermal and dermal innervation, based on PGP9.5 immunostaining, of SOD1(G93A) mice at different stages. The results showed a marked reduction of intraepidermal nerve fibers, Meissner's corpuscles, and subepidermal nerve density already at 4 weeks. This loss of innervation progressed over time. Dermal axonal density decreased at a later stage of the disease. There was a gradient of axonal loss, with a more severe decline in the epidermis compared with deeper structures, indicating a distal axonal neuropathy as the mechanism of degeneration. These findings suggest that the analysis of the cutaneous sensory innervation may be an accessible and useful tool to assess the neurodegeneration process in motoneuron diseases.
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PMID:Involvement of sensory innervation in the skin of SOD1(G93A) ALS mice. 2688 Jul 31