Effects of Palmitoylethanolamide on Neurodegenerative Diseases: A Review from Rodents to Humans
Abstract
:1. Introduction
1.1. PEA, an Anti-Inflammatory and Neuroprotective Substance
1.2. PEA Action in the Presence of Aging and Neurodegeneration
2. Mild Cognitive Impairment (MCI)
3. Alzheimer’s Disease (AD)
4. Parkinson’s Disease (PD)
5. Huntington’s Disease (HD)
6. Frontotemporal Dementia (FTD)
7. Amyotrophic Lateral Sclerosis (ALS)
8. Multiple Sclerosis (MS)
9. Other Diseases (Vascular Dementia, Myasthenia Gravis)
10. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Study | Disease | Sample | um PEA (Alone or In Combination) | Dosage | Duration | Main Outcomes of PEA Treatment |
---|---|---|---|---|---|---|
[47] | MCI | 1 patient | co-um-PEALut | 700/70 mg daily | T3: 3 months treatment T9: 9 months follow-up | T3: mild (though not significant) cognitive improvement; T9: near-normal neuropsychological assessment; improvement in test scores; brain SPECT near-normal. |
[48] | PD | 30 patients | PEA added to regular levodopa | 600 mg daily | 12 months | Progressive reduction in the total MDS-UPDRS score; reduction in most nonmotor and motor symptoms. |
[49] | PD | 1 patient | co-um-PEALut added to regular carbidopa/levodopa | 700/70 mg daily | 4 months | Complete resolution of leg and trunk dyskinesia and marked reduction in the onset of camptocormia during the “off” state. |
[50] | FTD | 17 patients | co-um-PEALut | 700 mg/2 daily | 4 weeks | Improvement in test scores and neurophysiological evaluation; increase in TMS-evoked frontal lobe activity and of high-frequency oscillations in the beta/gamma range. |
[51] | ALS | 1 patient | PEA | 600 mg/2 daily | ∼40 days | Improvement in clinical picture. |
[52] | ALS | 28 treated and 36 untreated patients | PEA + 50 mg riluzole or 50 mg riluzole only | 600 mg/2 daily | 6 months | Lower decrease in forced vital capacity over time as compared with untreated ALS patients. |
[53] | MS | 24 patients 17 healthy controls | eCBs levels in blood | _ | _ | eCB system is altered in MS. |
[54] | MS | 1 patient | PEA | 600 mg/2 daily | ∼9 months | Pain reduction; increased interval between acupuncture sessions. |
[55] | MS | 29 patients | PEA added to IFN-β1a or placebo | 600 mg daily | 12 months | Improvement in pain sensation, no reduction of erythema at the injection site, improved evaluation of quality of life, increase in PEA, AEA and OEA plasma levels, reduction of interferon-γ, tumor necrosis factor-α, and interleukin-17 serum profile. |
[56] | Myasthenia gravis | 22 patients | PEA | 600 mg/2 daily | 1 week | Reduced level of disability and decremental muscle response. |
Study | Disease | Sample | um PEA (Alone or In Combination) | Dosage | Duration | Main Outcomes of PEA Treatment |
---|---|---|---|---|---|---|
[57] | AD model (Aβ 1–42 intra-hippocampal injection) | Male adult Sprague-Dawley rats (9–12/group) | i.p. PEA PEA added to GW6471 | PEA:10 mg/kg; GW647: 2 mg/kg | 7 days | Restoration of Aβ 1–42-induced alterations; reduced mnestic deficits. |
[58] | AD model (Aβ 25–35 i.c.v. injection) | Male PPAR-α/(B6.129S4-SvJaePparatm 1Gonz) and WT mice (9–10/group) | s.c. PEA and GW7647 | PEA: 3–30 mg/kg daily, GW7647: 5 mg/kg daily | 1–2 weeks or a single dose | Reduction (10 mg/kg) or prevention (30 mg/kg) of behavioral impairments. No rescue of memory deficits. PEA acute treatment was ineffective. |
[59] | AD model | 3-month-old male 3 × Tg-AD and WT mice (9–10/group) | s.c. PEA or vehicle | 10 mg/kg daily | 90 days | Counteraction of disease progression, improvement of trophic support to neurons, in the absence of astrocytes and neuronal toxicity. |
[60] | AD model | 3-month-old or 9-month-old male 3 × Tg-AD or WT mice (7–11/group) | s.c. PEA or vehicle | 10 mg/kg daily | 90 days | Improvement of learning and memory, amelioration of depressive and anhedonia-like symptoms, reduced Aβ formation, tau protein phosphorylation, promotion of hippocampal neuronal survival and astrocytic function, rebalancing of glutamatergic transmission, restraint of neuroinflammation. |
[61] | AD model | 2-month-old male 3 × Tg-AD or WT mice (7–11/group) | oral PEA or vehicle | single dose/sub-chronic/chronic:100 mg/kg daily | 1–8–90 days | Rescue of cognitive deficit, restraint of neuroinflammation and oxidative stress, reduced increase in hippocampal glutamate levels. |
[62] | PD model (MPTP) | 6–7-week-old male PPAR-αKO PPAR-αWT mice (10/group) | i.p. PEA | 10 mg/kg | 8 days | Reduction of MPTP-induced microglial activation, glial fibrillary acidic protein positive expression astrocyte numbers, overexpression of S100b; protection against alterations in microtubule-associated protein 2a,b, dopamine transporter, nNOS-positive cells in the substantia nigra. Reversal of motor deficits. |
[63] | PD model (MPTP) | 3/21-month-old male CD1 mice (10/group) | oral PEA | 10 mg/kg | 60 days | Amelioration of behavioral deficits and of reduction of tyrosine hydroxylase and dopamine transporter in substantia nigra. Reduction of hippocampal proinflammatory cytokines and pro-neurogenic effects. |
[64] | PD model (6-OHDA) | Ten-week-old male Swiss CD1 mice (6 × group) | s.c. PEA or GW7647 | PEA 3–30 mg/kg/day; GW7647 5 mg/kg/day | 28 days | Improvement of behavioral impairment. Increased tyrosine hydroxylase expression at striatal level. Reduction in the expression of pro-inflammatory enzymes, protective scavenging effect. |
[65] | PD model (MPTP) | 8-week-old male C57BL/6 (10/group) | i.p. co-um-PEALut | 1 mg/kg daily | 8 days | Reduction of motor impairment, cataleptic response, immobility and anxiety levels. Reduction of neuronal degeneration and of specific PD markers, attenuation of inflammatory processes (activation of astrocytes, pro-inflammatory cytokines, and nitric oxide synthase), stimulation of autophagy. |
[66] | PD model (MPTP) | 8-week-old male C57BL/6 (10/group) | oral PEA-OXA or vehicle | 10 mg/kg daily | 8 days | Prevention of MPTP-induced bradykinesia and anxiety, and neuronal degeneration of the dopaminergic tract, prevention of dopamine depletion, modulation of microglia and astrocyte activation. |
[67] | HD model | ∼32-day-old-R6/2 10-week-old R6/2 mice and WT mice (4/group) | Measurement of PEA, AEA and 2-AG endogenous levels | _ | _ | Alteration of the eCB system, decreased levels of PEA in the striatum |
[68] | MS model (EAE) | 12-week-old female C57BL/6 (8/group) | i.p. PEA or CBD or in combination | PEA 5 mg/kg CBD 5 mg/kg | 3 days | Reduced severity of EAE neurobehavioral scores, diminished inflammation, demyelination, axonal damage and inflammatory cytokine expression. |
[69] | MS model (chronic relapsing EAE) | Biozzi ADH mice (>6/group) | i.v. or i.p. PEA | 1–10 mg/kg | Single injection | Amelioration of spasticity |
[70] | MS model (EAE) | C57BL/6 mice (8/group) | i.p. co-um-PEALut or vehicle | 0.1, 1, and 5 mg/kg | 16 days | Dose-dependent improvement of clinical signs through anti-inflammatory signals and pro-resolving circuits. |
[71] | MS model (TMEV-IDD) | Four-week female SJL/J mice | i.p. PEA or vehicle | 5 mg/kg | 10 days | Reduction of motor disability, anti-inflammatory effect. |
[72] | Vascular dementia | CD1 mice | Oral PEA-OXA or vehicle | 10 mg/kg daily | 15 days | Improvement of behavioral deficits, reduction of histological alterations, decrease of markers of astrocyte and microglia activation and oxidative stress, modulation of antioxidant response, inhibition of apoptotic process. |
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Landolfo, E.; Cutuli, D.; Petrosini, L.; Caltagirone, C. Effects of Palmitoylethanolamide on Neurodegenerative Diseases: A Review from Rodents to Humans. Biomolecules 2022, 12, 667. https://doi.org/10.3390/biom12050667
Landolfo E, Cutuli D, Petrosini L, Caltagirone C. Effects of Palmitoylethanolamide on Neurodegenerative Diseases: A Review from Rodents to Humans. Biomolecules. 2022; 12(5):667. https://doi.org/10.3390/biom12050667
Chicago/Turabian StyleLandolfo, Eugenia, Debora Cutuli, Laura Petrosini, and Carlo Caltagirone. 2022. "Effects of Palmitoylethanolamide on Neurodegenerative Diseases: A Review from Rodents to Humans" Biomolecules 12, no. 5: 667. https://doi.org/10.3390/biom12050667