Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029089 (ophthalmoplegia)
 3,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In mammalian cells, mitochondria provide energy from aerobic metabolism. They play an important regulatory role in apoptosis, produce and detoxify free radicals, and serve as a cellular calcium buffer. Neurodegenerative disorders involving mitochondria can be divided into those caused by oxidative phosphorylation (OXPHOS) abnormalities either due to mitochondrial DNA (mtDNA) abnormalities, e.g., chronic external ophthalmoplegia, or due to nuclear mutations of OXPHOS proteins, e.g., complex I and II associated with Leigh syndrome. There are diseases caused by nuclear genes encoding non-OXPHOS mitochondrial proteins, such as frataxin in Friedreich ataxia (which is likely to play an important role in mitochondrial-cytosolic iron cycling), paraplegin (possibly a mitochondrial ATP-dependent zinc metalloprotease of the AAA-ATPases in hereditary spastic paraparesis), and possibly Wilson disease protein (an abnormal copper transporting ATP-dependent P-type ATPase associated with Wilson disease). Huntingon disease is an example of diseases with OXPHOS defects associated with mutations of nuclear genes encoding non-mitochondrial proteins such as huntingtin. There are also disorders with evidence of mitochondrial involvement that cannot as yet be assigned. These include Parkinson disease (where a complex I defect is described and free radicals are generated from dopamine metabolism), amyotrophic lateral sclerosis, and Alzheimer disease, where there is evidence to suggest mitochondrial involvement perhaps secondary to other abnormalities.
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PMID:Mitochondria and degenerative disorders. 1157 22

We showed that humanin (HN), an endogenous peptide against Alzheimer disease-related insults, was expressed in muscles of patients with chronic progressive external ophthalmoplegia (CPEO), a major mitochondrial disease. Because HN was recently found to block proapoptotic Bax function and exert its versatile cytoprotective effects in association with an increase in ATP levels, HN expression may thus reflect a physiological response against degenerative changes in the muscles of patients with CPEO. We found HN expression in all four patients examined, each of whom had different mitochondrial DNA mutations including two different single DNA deletions, multiple deletions, and no major mutations detected. We also found that HN expression was not linked to focal cytochrome c deficiency, strongly associated with the subtype of CPEO with single deletions. These results suggest that HN expression is more closely related to degenerative changes in all types of CPEO. Notably, HN was also expressed in non-degenerative muscle fibers of patients with CPEO or Leigh syndrome, who had the 8993T>G mutation in the mitochondrial ATPase 6 gene known to be associated with impaired ATP synthesis. Collectively, our findings suggest that HN may be specifically expressed in response to defects in energy production in muscles with mitochondrial abnormalities.
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PMID:Humanin expression in skeletal muscles of patients with chronic progressive external ophthalmoplegia. 1663 4