Title : Cholinergic and glutamatergic alterations beginning at the early stages of Alzheimer disease: participation of the phospholipase A2 enzyme - Schaeffer_2008_Psychopharmacology.(Berl)_198_1 |
Author(s) : Schaeffer EL , Gattaz WF |
Ref : Psychopharmacology (Berl) , 198 :1 , 2008 |
Abstract :
RATIONALE: Alzheimer disease (AD), a progressive neurodegenerative disorder, is the leading cause of dementia in the elderly. A combination of cholinergic and glutamatergic dysfunction appears to underlie the symptomatology of AD, and thus, treatment strategies should address impairments in both systems. Evidence suggests the involvement of phospholipase A(2) (PLA(2)) enzyme in memory impairment and neurodegeneration in AD via actions on both cholinergic and glutamatergic systems. OBJECTIVES: To review cholinergic and glutamatergic alterations underlying cognitive impairment and neuropathology in AD and attempt to link PLA(2) with such alterations. METHODS: Medline databases were searched (no date restrictions) for published articles with links among the terms Alzheimer disease (mild, moderate, severe), mild cognitive impairment, choline acetyltransferase, acetylcholinesterase, NGF, NGF receptor, muscarinic receptor, nicotinic receptor, NMDA, AMPA, metabotropic glutamate receptor, atrophy, glucose metabolism, phospholipid metabolism, sphingolipid, membrane fluidity, phospholipase A(2), arachidonic acid, attention, memory, long-term potentiation, beta-amyloid, tau, inflammation, and reactive species. Reference lists of the identified articles were checked to identify additional studies of interest. RESULTS: Overall, results suggest the hypothesis that persistent inhibition of cPLA(2) and iPLA(2) isoforms at early stages of AD may play a central role in memory deficits and beta-amyloid production through down-regulation of cholinergic and glutamate receptors. As the disease progresses, beta-amyloid induced up-regulation of cPLA(2) and sPLA(2) isoforms may play critical roles in inflammation and oxidative stress, thus participating in the neurodegenerative process. CONCLUSION: Activation and inhibition of specific PLA(2) isoforms at different stages of AD could be of therapeutic importance and delay cognitive dysfunction and neurodegeneration. |
PubMedSearch : Schaeffer_2008_Psychopharmacology.(Berl)_198_1 |
PubMedID: 18392810 |
Schaeffer EL, Gattaz WF (2008)
Cholinergic and glutamatergic alterations beginning at the early stages of Alzheimer disease: participation of the phospholipase A2 enzyme
Psychopharmacology (Berl)
198 :1
Schaeffer EL, Gattaz WF (2008)
Psychopharmacology (Berl)
198 :1