StudyObjectives: PROK2isapeptideexpressedintheadultbrainmediatingneuroprotectivefunctions.PreviousstudiesreportedanupregulationofprokineticinsysteminParkinson’sdisease(PD),butevidenceinprodromalα-synucleinopathieswaslacking.Weinvestigatedtheexpressionofprokineticin-2(PROK2)anditsreceptors(PKR1andPKR2),alongwitholigomericα-synuclein(oligoα-syn)asamarkerofα-synucleinpathology,inolfactoryneurons(ONs)fromindividualswithidiopathicrapideyemovementsleepbehaviordisorder(iRBD). Methods: Olfactoryneurons,obtainedbynasalbrushfrom28idiopathicrapideyemovementsleepbehaviordisordersubjects(age:71.2±7.4years;males:89.3%;duration:4.9±2.5years)and28healthycontrols(HCs)(age:67.2±11.5years;males:64.2%),wereanalyzedusingreal-timepolymerase-chain-reaction(RT-PCR),immunofluorescence(IF),andwesternblot(WB).Inasubgroupofsubjects,resultswerevalidatedinserum. Results: Intheidiopathicrapideyemovementsleepbehaviordisordergroup,prokineticin-2proteinexpressionwasreducedinbothONs(immunofluorescence:F(1,26)=15.289,p<.001;westernblot:F(1,12)=9.073,p=.011)andserumcomparedwithHCs(westernblot:F(1,12)=4.557,p=.050).IdiopathicrapideyemovementsleepbehaviordisordersubjectsshowedlowermRNAexpressionofprokineticinreceptorscomparedwithhealthycontrols(real-timepolymerase-chain-reactionforprokineticinreceptor-1:F(1,26)=16.131,p<.001;real-timepolymerase-chain-reactionforprokineticinreceptor-2:F(1,39)=4.946,p=.032).Oligoα-synaccumulationinolfactoryneuronswashigherinidiopathicrapideyemovementsleepbehaviordisorderthanhealthycontrols,yetthedifferenceonlytendedtostatisticalsignificance(immunofluorescence:F(1,18)=3.169,p=.092). Conclusions: IncontrastwithfindingsinParkinson’sdisease,wefoundadownregulationofprokineticinsysteminidiopathicrapideyemovementsleepbehaviordisorder.Thecausesofprokineticinsystemdownregulationinthisprodromalstagemaybemultiple.Theabsenceofclearoligoα-synaccumulation,knowntriggerofprokineticin-2,mayplayarole.Ontheotherhand,alackofactivationofthissystemmightactaspredisposingfactorforthedevelopmentofidiopathicrapideyemovementsleepbehaviordisorderand,subsequently,full-blownneurodegeneration.
The Prokineticin system is downregulated in idiopathic rapid eye movement sleep behavior disorder. Evidence from olfactory neurons / Grillo, P., Maftei, D., Calculli, A., Schirinzi, T., Mauramati, S., Vincenzi, M., Di Certo, M.G., Gabanella, F., Di Martino, D., Benazzo, M., Severini, C., Lattanzi, R., Pisani, A., Terzaghi, M.. - In: SLEEP. - ISSN 0161-8105. - 49:4(2026), pp. 1-9. [10.1093/sleep/zsag006]
The Prokineticin system is downregulated in idiopathic rapid eye movement sleep behavior disorder. Evidence from olfactory neurons
Grillo, Piergiorgio;Maftei, Daniela;Calculli, Alessandra;Vincenzi, Martina;Severini, Cinzia;Lattanzi, Roberta;
2026
Abstract
StudyObjectives: PROK2isapeptideexpressedintheadultbrainmediatingneuroprotectivefunctions.PreviousstudiesreportedanupregulationofprokineticinsysteminParkinson’sdisease(PD),butevidenceinprodromalα-synucleinopathieswaslacking.Weinvestigatedtheexpressionofprokineticin-2(PROK2)anditsreceptors(PKR1andPKR2),alongwitholigomericα-synuclein(oligoα-syn)asamarkerofα-synucleinpathology,inolfactoryneurons(ONs)fromindividualswithidiopathicrapideyemovementsleepbehaviordisorder(iRBD). Methods: Olfactoryneurons,obtainedbynasalbrushfrom28idiopathicrapideyemovementsleepbehaviordisordersubjects(age:71.2±7.4years;males:89.3%;duration:4.9±2.5years)and28healthycontrols(HCs)(age:67.2±11.5years;males:64.2%),wereanalyzedusingreal-timepolymerase-chain-reaction(RT-PCR),immunofluorescence(IF),andwesternblot(WB).Inasubgroupofsubjects,resultswerevalidatedinserum. Results: Intheidiopathicrapideyemovementsleepbehaviordisordergroup,prokineticin-2proteinexpressionwasreducedinbothONs(immunofluorescence:F(1,26)=15.289,p<.001;westernblot:F(1,12)=9.073,p=.011)andserumcomparedwithHCs(westernblot:F(1,12)=4.557,p=.050).IdiopathicrapideyemovementsleepbehaviordisordersubjectsshowedlowermRNAexpressionofprokineticinreceptorscomparedwithhealthycontrols(real-timepolymerase-chain-reactionforprokineticinreceptor-1:F(1,26)=16.131,p<.001;real-timepolymerase-chain-reactionforprokineticinreceptor-2:F(1,39)=4.946,p=.032).Oligoα-synaccumulationinolfactoryneuronswashigherinidiopathicrapideyemovementsleepbehaviordisorderthanhealthycontrols,yetthedifferenceonlytendedtostatisticalsignificance(immunofluorescence:F(1,18)=3.169,p=.092). Conclusions: IncontrastwithfindingsinParkinson’sdisease,wefoundadownregulationofprokineticinsysteminidiopathicrapideyemovementsleepbehaviordisorder.Thecausesofprokineticinsystemdownregulationinthisprodromalstagemaybemultiple.Theabsenceofclearoligoα-synaccumulation,knowntriggerofprokineticin-2,mayplayarole.Ontheotherhand,alackofactivationofthissystemmightactaspredisposingfactorforthedevelopmentofidiopathicrapideyemovementsleepbehaviordisorderand,subsequently,full-blownneurodegeneration.| File | Dimensione | Formato | |
|---|---|---|---|
|
Grillo_prokineticin-system_2026.pdf
accesso aperto
Tipologia:
Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza:
Creative commons
Dimensione
1.17 MB
Formato
Adobe PDF
|
1.17 MB | Adobe PDF |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
