Linked Life Data

12604663

Source:http://linkedlifedata.com/resource/pubmed/id/12604663

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-2-26
pubmed:abstractText
Enormous effort is now being devoted to developing drugs that slow neurodegeneration in Alzheimer's disease (AD), although insights into AD genetics and molecular pathogenesis only arose in the last 15 years. Acetylcholinesterase inhibitors that temporarily slow loss of cognitive function remain the only approved AD drugs. Discovery of mutations in three genes leading to severe early onset AD was critical in focusing attention on the role of amyloid peptides (Abeta) in neuronal cell death, and enhanced understanding of the biology of these peptides has led to an array of mechanism-based drug discovery strategies. These include inhibitors for Abeta-generating proteases, agents that prevent or reverse Abeta oligomerization, immunotherapies to reduce Abeta in brain and plasma, and drugs to modulate cholesterol-mediated effects on Abeta transport. Strategies are also underway to minimize toxic effects of Abeta fibrils on neurons, and these include antioxidants, blockers of glutamate-mediated excitotoxicity, and modulators of inflammatory responses within the brain. Although several approaches involve new agents for recently discovered targets, many are based on new applications of existing drugs such as statins and nonsteroidal anti-inflammatory drugs. Discovery of abnormally phosphorylated tau protein in neurofibrillary tangles in AD brain has led to strategies for identifying selective inhibitors of tau kinases and central nervous system/brain-permeable drugs that help maintain microtubule integrity. Clearly, a large gap exists between our understanding of the cellular cascades targeted in drug discovery and widespread failure of the nervous system that AD represents. Nevertheless, the pace of recent research clearly supports optimism that slowing progression of AD will soon be possible.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
304
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
897-904
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Drugs targeting Alzheimer's disease: some things old and some things new.
pubmed:affiliation
Department of Pharmacology and Toxicology, University of Kansas, Lawrence, Kansas 66045-7582, USA. mlm@ku.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review