Phospholipase A2 activation as a therapeutic approach for cognitive enhancement in early-stage Alzheimer disease.
BACKGROUND
Alzheimer disease (AD) is the leading cause of dementia in the elderly and has no known cure. Evidence suggests that reduced activity of specific subtypes of intracellular phospholipases A2 (cPLA2 and iPLA2) is an early event in AD and may contribute to memory impairment and neuropathology in the disease.


OBJECTIVE
The objective of this study was to review the literature focusing on the therapeutic role of PLA2 stimulation by cognitive training and positive modulators, or of supplementation with arachidonic acid (PLA2 product) in facilitating memory function and synaptic transmission and plasticity in either research animals or human subjects.


METHODS
MEDLINE database was searched (no date restrictions) for published articles using the keywords Alzheimer disease (mild, moderate, severe), mild cognitive impairment, healthy elderly, rats, mice, phospholipase A(2), phospholipid metabolism, phosphatidylcholine, arachidonic acid, cognitive training, learning, memory, long-term potentiation, protein kinases, dietary lipid compounds, cell proliferation, neurogenesis, and neuritogenesis. Reference lists of the identified articles were checked to select additional studies of interest.


RESULTS
Overall, the data suggest that PLA2 activation is induced in the healthy brain during learning and memory. Furthermore, learning seems to regulate endogenous neurogenesis, which has been observed in AD brains. Finally, PLA2 appears to be implicated in homeostatic processes related to neurite outgrowth and differentiation in both neurodevelopmental processes and response to neuronal injury.


CONCLUSIONS
The use of positive modulators of PLA2 (especially of cPLA2 and iPLA2) or supplementation with dietary lipid compounds (e.g., arachidonic acid) in combination with cognitive training could be a valuable therapeutic strategy for cognitive enhancement in early-stage AD.
Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Rua Dr. Ovídio Pires de Campos 785, 05403-010 São Paulo, SP, Brazil. schaffer@usp.br
Evelin L
EL
Schaeffer
Orestes V
OV
Forlenza
Wagner F
WF
Gattaz
D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology / Q000523:psychology*; D016229:Amyloid beta-Peptides / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003071:Cognition / Q000187:drug effects*; D004041:Dietary Fats / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007858:Learning / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy / Q000201:enzymology; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D018697:Nootropic Agents / Q000494:pharmacology*; D054467:Phospholipases A2 / Q000378:metabolism* / Q000502:physiology
D016229:Amyloid beta-Peptides; D004041:Dietary Fats; D018697:Nootropic Agents; D054467:Phospholipases A2