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Targeting NAAA counters dopamine neuron loss and symptom progression in mouse models of parkinsonism

Francesca Palese, Silvia Pontis, Natalia Realini, Alexa Torrens, Faizy Ahmed, Francesca Assogna, Clelia Pellicano, Paola Bossù, Gianfranco Spalletta, Kim Green, Daniele Piomelli. Pharmacol Res. 2022 Aug:182:106338.

Laboratory studyHumansOther animalsWith NAAA gene deletion or NAAA inhibitors, which raise the body's own palmitoylethanolamide; PEA itself was not given

This study tested palmitoylethanolamide together with NAAA gene deletion or NAAA inhibitors, which raise the body's own palmitoylethanolamide; PEA itself was not given. Its results cannot be assigned to palmitoylethanolamide alone. More combination studies.

Design
Laboratory study
Subjects
Human SH-SY5Y cells; mice given 6-OHDA or MPTP; post-mortem brain cortex and blood exosomes from people with Parkinson's disease and age-matched controls
Dose used in the study
Not stated in the abstract
Duration
Not stated in the abstract
What was measured
NAAA expression and palmitoylethanolamide content in cells and mouse midbrain; dopamine neuron death and parkinsonian symptoms in mice; NAAA levels in human brain and blood samples

What the authors reported

The toxins raised NAAA and lowered PEA in cells and mouse dopamine neurons. Deleting the Naaa gene or inhibiting NAAA substantially reduced dopamine neuron death and parkinsonian symptoms in mice, and NAAA was higher in brain cortex and blood exosomes from people with Parkinson's disease than in controls.

Limits of this study

Mouse and cell work plus human tissue measurements; it cannot show effect in people treated in practice, and no palmitoylethanolamide was given. The senior author holds patents on NAAA inhibitors.

Source

PubMed 35781057 · doi:10.1016/j.phrs.2022.106338

Entry checked against the abstract on PubMed on 2026-09-22. The dose shown is the dose the researchers used. It is not a recommendation. How to read this page.