Linked Life Data

15670741

Source:http://linkedlifedata.com/resource/pubmed/id/15670741

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-1-26
pubmed:abstractText
gamma-Secretase cleavage of the amyloid precursor protein already subjected to a prior beta-secretase cleavage generates beta-amyloid (Abeta) peptide fragments, which are major constituents of the amyloid plagues found in Alzheimer's disease brain tissues. gamma-Secretase activity and components of the gamma-secretase complex are found in the endoplasmic reticulum-Golgi intermediate compartment, the Golgi, the trans-Golgi network, the plasma membrane, the endosomal-lysosomal system and recently, the mitochondria. Abeta fragments have been shown to be neurotoxic, leading to mitochondrial dysfunction and enhanced apoptotic cell death. However, if Abeta fragments are indeed detrimental to neurons, the widespread presence of enzymatic activity that would result in their generation in the cell appears to make little sense. The presence of a gamma-secretase complex in the mitochondrion, an organelle that is particularly susceptible to Abeta toxicity, is even more puzzling. Emerging evidence suggests that both secreted and intracellular Abeta fragments have endogenous functions. Also, while the fibrillogenic Abeta1-42 is clearly neurotoxic, the more abundant and soluble Abeta1-40 is an antioxidant and could potentially be neuroprotective in several ways. A "physiological" amount of Abeta1-40 production by cellular gamma-secretase activity may be part of the neuron's natural counter against oxidative damage, in addition to endogenous roles in neuronal survival and modulation of synaptic transmission. In any case, whether Abeta is produced locally in the mitochondria and the function for mitochondrial Abeta, if produced, is yet unclear.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-291X
pubmed:author
pubmed:issnType
Print
pubmed:day
4
pubmed:volume
328
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1-5
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Widespread gamma-secretase activity in the cell, but do we need it at the mitochondria?
pubmed:affiliation
Department of Biochemistry and Programme in Neurobiology and Aging, National University of Singapore, 8 Medical Drive, Singapore 117597, Singapore.
pubmed:publicationType
Journal Article, Review