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 A2 (PLA2) 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 PLA2 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 A2, arachidonic acid, attention, memory, long-term potentiation, β-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 cPLA2 and iPLA2 isoforms at early stages of AD may play a central role in memory deficits and β-amyloid production through down-regulation of cholinergic and glutamate receptors. As the disease progresses, β-amyloid induced up-regulation of cPLA2 and sPLA2 isoforms may play critical roles in inflammation and oxidative stress, thus participating in the neurodegenerative process.
Conclusion
Activation and inhibition of specific PLA2 isoforms at different stages of AD could be of therapeutic importance and delay cognitive dysfunction and neurodegeneration.
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References
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Schaeffer, E.L., Gattaz, W.F. Cholinergic and glutamatergic alterations beginning at the early stages of Alzheimer disease: participation of the phospholipase A2 enzyme. Psychopharmacology 198, 1–27 (2008). https://doi.org/10.1007/s00213-008-1092-0
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DOI: https://doi.org/10.1007/s00213-008-1092-0