Phospholipase A2 activation as a therapeutic approach for cognitive enhancement in early-stage Alzheimer disease

Schaeffer, Evelin L.; Forlenza, Orestes Vicente; Gattaz, Wagner F.

doi:10.1007/s00213-008-1351-0

Cited by 62 publications

(31 citation statements)

References 176 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, it is plausible to suggest that higher Pla2 activity, or specifically the iPla2 subgroup, could play a key role in the genesis of a better memory retrieval, which in our study was observed in animals treated with lithium. Furthermore, our group recently demonstrated that rats fed with a high conjugated linoleic acid diet (which modulates PLA2 activity) showed increased memory and higher hippocampal PLA2 levels [83], in line with other groups that showed the positive impact of polyunsaturated fatty acids and memory in elderly subjects [84,85].…”

Section: Discussionsupporting

confidence: 83%

Lithium activates brain phospholipase A2 and improves memory in rats: implications for Alzheimer’s disease

Mury

Silva

Barbosa

et al. 2015

Eur Arch Psychiatry Clin Neurosci

Self Cite

View full text Add to dashboard Cite

a significant perdurability of long-term memory, which correlated with increased transcriptional and enzymatic activities of certain members of the Pla2 family (iPla2 and sPla2) after the chronic lithium treatment. Our data suggest new possible targets of lithium, add more information on its pharmacological activity and reinforce the possible use of low doses of lithium for the treatment of neurodegenerative conditions such as the Alzheimer's disease.

show abstract

Section: Discussionsupporting

confidence: 83%

Lithium activates brain phospholipase A2 and improves memory in rats: implications for Alzheimer’s disease

Mury

Silva

Barbosa

et al. 2015

Eur Arch Psychiatry Clin Neurosci

Self Cite

View full text Add to dashboard Cite

show abstract

“…Consistently, the predominant PLA 2 activity in rodent hippocampal slices was reported to be manifested by iPLA 2 and to be essential for synaptic plasticity , as refl ected in iPLA 2 inhibition studies ( 311 ). This was later confi rmed in whole animal studies ( 141 ), leading to the suggestion that reductions in cPLA 2 and iPLA 2 activities can have adverse effects on memory in patients with Alzheimer's ( 312 ). These studies, however, did not distinguish which iPLA 2 ( ␤ or ␥ ) isoform activity was critical for the dementia associated with targeted genetic knockdowns ( 373 ) …”

Section: Ipla 2 ␤ and Diseasesmentioning

confidence: 99%

Calcium-independent phospholipases A2 and their roles in biological processes and diseases

Ramanadham

Ali

Ashley

et al. 2015

Journal of Lipid Research

169

190

View full text Add to dashboard Cite

The Ca 2+ -independent phospholipases A 2 (iPLA 2 s) are part of a diverse family of PLA 2 s that hydrolyze the sn -2 substituent from membrane phospholipids to release a free fatty acid and a lysolipid ( 1, 2 ). These enzymes are ubiquitously expressed, and in contrast to secretory PLA 2 s (sPLA 2 s) and cytosolic PLA 2 s (cPLA 2 s), do not require Ca 2+ for either translocation or activity. Some of the fi rst descriptions of iPLA 2 activity were in the mid-to late-1980s with the identifi cation of a plasmalogen-selective PLA 2 in Abstract Among the family of phospholipases A 2 (PLA 2 s) are the Ca 2+ -independent PLA 2 s (iPLA 2 s) and they are designated group VI iPLA 2 s. In relation to secretory and cytosolic PLA 2 s, the iPLA 2 s are more recently described and details of their expression and roles in biological functions are rapidly emerging. The iPLA 2 s or patatin-like phospholipases (PNPLAs) are intracellular enzymes that do not require Ca 2+ for activity, and contain lipase (GXSXG) and nucleotide-binding (GXGXXG) consensus sequences. Though nine PNPLAs have been recognized, PNPLA8 (membraneassociated iPLA 2 ␥ ) and PNPLA9 (cytosol-associated iPLA 2 ␤ ) are the most widely studied and understood. The iPLA 2 s manifest a variety of activities in addition to phospholipase, are ubiquitously expressed, and participate in a multitude of biological processes, including fat catabolism, cell differentiation, maintenance of mitochondrial integrity, phospholipid remodeling, cell proliferation, signal transduction, and cell death. As might be expected, increased or decreased expression of iPLA 2 s can have profound effects on the metabolic state, CNS function, cardiovascular performance, and cell survival; therefore, dysregulation of iPLA 2 s can be a critical factor in the development of many diseases. This review is aimed at providing a general framework of the current understanding of the iPLA 2 s and discussion of the potential mechanisms of action of the iPLA 2 s and related involved lipid mediators. -Ramanadham, S

show abstract

“…Since cholinergic neurons influence the neurocognitive attentional function of rodents and humans, cholinergic drugs (acetylcholine esterase inhibitors) or NGF gene injection into BCNs have improved attention deficits and cerebral metabolism in early-stage AD [5,7,46,47,48,49]. Of the six components, the go/no-go is known as ‘inhibition control’, a conduct that inhibits inappropriate responses and regulates impulsions [36].…”

Section: Discussionmentioning

confidence: 99%

“…Among the main nonmemory neurocognitive impairments during the initial stage of AD or during amnestic mild cognitive impairment (A-MCI), executive dysfunction and attentional impairment have been shown to occur before deficits in language and visuospatial function, with the progression of cholinergic neuron degeneration beginning during the early phase [1,2,3,4,5,6,7]. From a longitudinal aspect, MCI patients with memory and executive function/psychomotor speed deficits have a higher risk of converting to AD than patients with only memory deficits [8].…”

Section: Introductionmentioning

confidence: 99%

Association between Nerve Growth Factor Gene Polymorphism and Executive Dysfunction in Japanese Patients with Early-Stage Alzheimer’s Disease and Amnestic Mild Cognitive Impairment

Nagata

Shinagawa

Nukariya

et al. 2011

Dement Geriatr Cogn Disord

View full text Add to dashboard Cite

Background/Aims: To address the clinical neurocognitive roles of nerve growth factor (NGF) genetic polymorphism in early-stage Alzheimer’s disease (AD) and amnestic mild cognitive impairment (A-MCI), we investigated the association between this single-nucleotide polymorphism (SNP) and executive dysfunction as a nonmemory cognitive impairment. Methods: Among 200 outpatients with dementia and MCI whose NGF SNP rs6330 genotype was identified, those with A-MCI (n = 35) and early-stage AD (n = 67) were recruited and divided into three groups according to genotype (C/C: n = 58, C/T: n = 39, T/T: n = 5). Then, the Frontal Assessment Battery (FAB) scores were compared among the three (C/C, C/T, T/T) or two (C/C, T carrier) genotype groups. Results: Among the subtests, a significant difference was only noted for the go/no-go scores (p < 0.01) between C/C and T carriers. However, no significant differences in the demographic variables and other neuropsychological subtest scores reflecting attentional and memory function were observed among the genotypes. Conclusion: Regarding the functional roles of neurotrophin polymorphisms as they relate to executive dysfunction, the NGF gene rs6330 might influence the inhibition task in Japanese patients with early-stage AD or A-MCI.

show abstract

Phospholipase A2 activation as a therapeutic approach for cognitive enhancement in early-stage Alzheimer disease

Abstract: 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.

Cited by 62 publications

References 176 publications

Lithium activates brain phospholipase A2 and improves memory in rats: implications for Alzheimer’s disease

Lithium activates brain phospholipase A2 and improves memory in rats: implications for Alzheimer’s disease

Calcium-independent phospholipases A2 and their roles in biological processes and diseases

Association between Nerve Growth Factor Gene Polymorphism and Executive Dysfunction in Japanese Patients with Early-Stage Alzheimer’s Disease and Amnestic Mild Cognitive Impairment

Contact Info

Product

Resources

About