Neuroinflammation and synaptic dysfunction in Alzheimer’s disorder (AD) have been acknowledged as epiphenomena with inflammation and modified neurotransmission happening when disabled neurons excite glia activation and variations in neuron biology. Specifically, it is now well established that the pathogenesis of AD includes also interactions with immunological mechanisms/responses in the brain.
Neuroinflammation in AD is predominantly linked to the central nervous system (CNS)-resident microglia, astroglia, and perivascular macrophages, which have been implicated at the cellular level.
Regional inflammatory responses characterize the CNS in AD, with deposits of β-amyloid (Aβ) as foci, associated with increased expression of pro-inflammatory cytokines, acute-phase proteins, and complement components, along with signs of activated microglia and reactive astrocytes.
AN OVERVIEW OF PALMITOYLETHANOLAMIDE:
Palmitoylethanolamide (PEA) is both a naturally occurring lipid ingredient contained in foods/dietary supplements and an endogenous lipid mediator belonging to the class of fatty acid ethanol amides.
Evidence indicates that PEA is an important anti-inflammatory, analgesic, and neuroprotective mediator acting on several molecular targets in both central and peripheral organs and systems. However, PEA lacks a primary antioxidant potential to inhibit the development of available radicals and to prevent the suffering of DNA, lipids, and proteins.
PEA attracted the interest of the scientific community mainly after the discovery by an Italian Nobel Prize laureate Rita Levi Montalcini and co-workers that some acylethanolamines, initially termed ALIA-amides are endogenously amalgamated lipids using exceptional anti-inflammatory attributes.
It belongs to the class of non-endocannabinoid NAE, which also includes stearoyl ethanolamide (C18:0 N-acylethanolamine), oleoyl-ethanolamide (OEA, C18:1 N-acylethanolamine), and linoleoylethanolamide (C18:2 N-acylethanolamine). These compounds are much more abundant than the endocannabinoid anandamide in several animal tissues and endowed with important biological actions.
PALMITOYLETHANOLAMIDE AND ALZHEIMER’S DISEASE
Various preclinical and amazing clinical evidence confirms the prospect of PEA as a therapeutic tool with great potential for the efficient operation of complex pathologies distinguished by neurodegeneration and neuroinflammation.
MECHANISM OF ACTION OF PEA: FOCUS ON NEUROINFLAMMATION
- Several preclinical studies have demonstrated that PEA can induce its biological effects by acting on several molecular targets in both central and peripheral nervous systems. As reported above, it has been initially suggested that PEA, belonging to the class of acylethanolamines, exerts its anti(neuro)inflammatory effects by acting as an “autacoid local injury antagonist” (ALIA).
- However, subsequent preclinical studies strongly supported the view that PEA can directly activate at least two different receptors: the peroxisome proliferator-activated receptor-alpha and the orphan GPCR 55.
- Practiced together, the earlier decisions firmly recommend that PEA by stimulating multifactorial pharmacological purposes and by negotiating diverse cellular mediators could perform assuring guarding roles in conflicting neuroinflammation and neurodegeneration. The ability of PEA to synergistically interact via several mechanisms is attributed to the compound’s unique properties concerning the traditional anti-inflammatory drugs.
CONCLUSION AND RESULTS:
Finally, PEA has proven efficacious in humans in several clinical settings, and none of the clinical trials with PEA like Pterostilbene at https://www.cofttek.com/product/537-42-8/ to date have reported treatment-related adverse events.
