Effects of Palmitoylethanolamide on Neurodegenerative Diseases: A Review from Rodents to Humans

Abstract

Palmitoylethanolamide (PEA) stands out among endogenous lipid mediators for its neuroprotective, anti-inflammatory, and analgesic functions. PEA belonging to the N-acetylanolamine class of phospholipids was first isolated from soy lecithin, egg yolk, and peanut flour. It is currently used for the treatment of different types of neuropathic pain, such as fibromyalgia, osteoarthritis, carpal tunnel syndrome, and many other conditions. The properties of PEA, especially of its micronized or ultra-micronized forms maximizing bioavailability and efficacy, have sparked a series of innovative research to evaluate its possible application as therapeutic agent for neurodegenerative diseases. Neurodegenerative diseases are widespread throughout the world, and although they are numerous and different, they share common patterns of conditions that result from progressive damage to the brain areas involved in mobility, muscle coordination and strength, mood, and cognition. The present review is aimed at illustrating in vitro and in vivo research, as well as human studies, using PEA treatment, alone or in combination with other compounds, in the presence of neurodegeneration. Namely, attention has been paid to the effects of PEA in counteracting neuroinflammatory conditions and in slowing down the progression of diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Frontotemporal dementia, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis. Literature research demonstrated the efficacy of PEA in addressing the damage typical of major neurodegenerative diseases.

Effect of Ultra-Micronized Palmitoylethanolamide and Luteolin on Olfaction and Memory in Patients with Long COVID: Results of a Longitudinal Study

“…The decreased ROS also improves mitochondrial function, ameliorating the brain environment and facilitating the recovery of neuronal connections [ 30 ]. In preclinical studies of neuroinflammatory disorders, co-ultra-micronized PEA and luteolin improve neuroprotection compared with either molecule alone [ 31 , 32 , 33 ].…”

The Beneficial Effects of Ultramicronized Palmitoylethanolamide in the Management of Neuropathic Pain and Associated Mood Disorders Induced by Paclitaxel in Mice

“…Neuroinflammation is a localized inflammation occurring in the PNS and CNS in response to trauma, bacterial/viral infection, autoimmunity, and/or toxins [ 83 , 84 ]. In particular, neuroinflammation is a common feature across different conditions, including neurodegenerative diseases, fibromyalgia, and chronic pain [ 83 , 85 , 86 ]. Different studies have reported the effect of PEA in the management of pain and inflammatory conditions [ 87 , 88 , 89 ].…”

Therapeutic effect of palmitoylethanolamide in cognitive decline: A systematic review and preliminary meta-analysis of preclinical and clinical evidence

“…This is the first systematic review of all studies investigating the biobehavioral effects of palmitoylethanolamide (PEA) with reference to cognitive decline, that is the core symptomatologic domain of neurocognitive disorders (NCDs) ( 4 ). Independently of potential effects of PEA on additional features of NCDs, such as motor impairments, pain, and overall disability [recently reviewed here ( 57 )], disentangling whether PEA is effective in improving cognition, possibly corroborated by evidence of a restoring effect on its neurobiological underpinnings, is of paramount importance to tip the scales toward considering PEA an adjunctive therapeutic option for NCDs. Based on evidence that degeneration of basal forebrain neurons causes a loss of cholinergic tone in the basal forebrain cholinergic system, with implications for the development of cognitive decline ( 58 ), most research has focused on the role of acetylcholinesterase (AChE) inhibitors as a potential treatment for NCDs ( 59 ).…”