Curcumin Derivative J-147: O se Togafitiga Folafolaga mo le Fa'ama'i o le Alzheimer, Anti-Atua, ma le Ma'i Fa'anoanoa Tele (MDD)

2. Aoao atili e uiga i le J-147 Galuega (Mechanism)
3. Fa'amanuiaga Va'ai vave o le J-147
4.J-147 Togafiti le Fa'ama'i o le Alzheimer(AD)
5.J-147 Togafiti le Faafitauli o le Matua
6.J-147 To'a'i ma'i fa'anoanoa tele(MDD)
7. More Su'esu'ega E uiga i le J-147
8. O fea e fa'atau ai J-147 Pa'u
9.Telefoni
J-147 Faʻamatalaga
Curcumin o se polyphenol ma o le vaega ola o Turmeric ma Ginger. O Curcumin e tele faʻamanuiaga aoga i le togafitia o le tele o faʻamaʻi, ae ona o lona le lelei gafatia e sopoʻia le Blood-Brain Barrier (BB), o loʻo manino tapulaʻa.
Lona uiga, J147 (CAS:1146963-51-0) o le Curcumin ma Cyclohexyl-Bisphenol A (CBA) mafuaʻaga lea o se malosi neurogenic ma neuroprotective vailaʻau. Na atiaʻe mo le faʻaaogaina o le togafitia o neurodegenerative tuʻufaʻatasia ma le matua. E mafai e le J147 ona kolosi le BBB ile faiʻai (malosi) ma faʻamalosia le faʻatupuina ole sela o neura.
E le pei o fualaʻau nei ua faʻamaonia mo le Alzheimer's Disease, o le J147 e le o se mea e taofi ai le acetylcholinesterase poʻo se tagata e taofiofia ai le phosphodiesterase, ae e faʻamalosia ai le malamalama ma se togafitiga puʻupuʻu
I lenei pou, o le a tatou talanoaina ai pe faʻafefea e le curcumin derivative J147 ona togafitia le Alzheimer's Disease (AD), faʻafitauli ogaoga o le mafaufau (MDD) ma le Aneti-ua matua.
O mea nei:
- Aʻoaʻo atili e uiga i le J-147 Work (Mechanism)
- Vave Vaaia Faamanuiaga o le J-147
- J-147 Togafitiga Faʻamaʻi o le Alzheimer (AD)
- J-147 Togafitiga Faʻafitauli o le Matua
- J-147 Togafitiga Sili faʻafitauli o le mafaufau (MDD)
- Sili atu Suesuega E uiga i le J-147
- O fea e faʻatau ai le paʻu J-147
Aʻoaʻo atili e uiga i le J-147 Work (Mechanism)
Seia le 2018, o le J-147 aafiaga i luga o le sela na tumau pea le le malamalama seʻia oʻo i le Salk Institute Neurobiologists faʻamamaina le paso. O le vailaʻau e galue i le fusifusia i le ATP synthase. O lenei mitochondrial protein suia ai le gaosiaina o le malosi o le sela, o le mea lea, faʻatonutonu ai le gasologa o le soifua matua.
J-147 auala o gaioiga o le a faʻalauteleina ai foi le maualuga o le tele o neurotransmitters e aofia ai NGF ma BDNF. E le gata i lea, e galue i luga o le beta-amyloid maualuga, e masani ona maualuga i tagata mamaʻi ma le Alzheimer ma le mafaufau. O aʻafiaga ole J-147 e aofia ai le faʻatelegese ole alualu i luma ole Alzheimer, puipuia le le lava o mea e manatua, ma le faʻateleina ole gaosia o sela o le neuronal.
AASraw o le tagata poto faapitoa gaosi oloa o Curcumin Derivative J-147.
Faʻamolemole kiliki ii mo upusii faʻamatalaga:
Faʻafesoʻotaʻi matou
Vave Vaaia Faamanuiaga o le J-147
'Faʻaleleia le Mitochondrial Function Ma Longevity
'Puipui le Faʻamaʻi ole Alzheimer
'Faaleleia le manatuaina
❹ Tupu le Faiʻai
'Puipuia Neurons
❻ Atonu Faʻaleleia le Maʻi suka
'Tauivi ma le tiga ma Neuropathy
❽ Atonu Faʻaleleia le popole
J-147 Togafitiga Faamaʻi o le Alzheimer (AD)
J-147 ma le AD: Talaʻaga
I le taimi nei, o le tele fualaʻau mauaina faʻafitauli mo neurodegenerative faʻamaʻi e faʻavae luga maualuga afinaga ligands mo tasi faʻamaʻi-faʻapitoa sini. Mo le faʻamaʻi o le Alzheimer (AD), o le taulaʻiga o le amyloid beta peptide (Ass) e faʻatonutonu faʻamaʻi o le aiga Alzheimer. Peitai, talu ai o lena tausaga o le sili tele tulaga lamatia mo AD, na matou suʻesuʻeina se isi vailaʻau saili togafiti lea e faʻavae i luga o le aoga i le tele sela sela agavaiʻa o tausaga-fesoʻotaʻi pathologies nai lo naʻo amyloid metabolism. I le faʻaaogaina ai o lenei auala, na matou faʻailoa ai le sili atu le malosi, faʻaaogaina i le gaioiga, neurotrophic molemole e faʻafaigofie ai le manatuaina o mea masani o meʻa, ma puipuia ai le leiloa o synaptic proteins ma faʻaleagaina mafaufau i le transgenic AD mouse model.
J 147 ma le AD: Suʻesuʻega o faʻamatalaga faʻavae i Isumu
FOLASAGA: E ui i le tele o tausaga o suʻesuʻega, e leai ni vailaʻau e suia ai faʻamaʻi mo le gasegase o le Alzheimer (AD), o se faʻamaʻi oti ua leva ona aafia i le neurodegenerative. Suʻesuʻega mo togafitiga talafeagai i rodent models o le AD e masani ona faʻalagolago ile suʻesuʻeina o vailaʻau aʻo leʻi i ai faʻamaʻi, ma faʻataʻitaʻia ai faʻamaʻi puipuia nai lo faʻamaʻi suiga. E le gata i lea, o lenei auala i le suʻesuʻega e leʻo atagia mai ai le faʻataʻitaʻiina o gasegase AD lea e mafai ona faʻamatalaina le le mafai ona faʻaliliu upu tuʻufaʻatasia e aoga tele i manu faʻataʻitaʻi i faʻafitauli o faʻamaʻi i vailaʻau. E manino lava o se sili atu auala i le muaʻi falemaʻi vailaʻau suʻesuʻega mo AD e manaʻomia.
METHODS: Ina ia sili atu ona atagia le faʻatulagaina ole falemaʻi, na matou faʻaaogaina se isi suʻega faʻataʻitaʻiga e aofia ai le togafitia o AD isumu i le laʻasaga ole faʻamaʻi pe a oʻo ina faʻataʻitaʻi ua uma ona alualu i luma. Matua (20-masina le matua) transgenic AD isumu (APP / swePS1DeltaE9) na fafagaina se sili atu le malosi, tautala gaioiga, manatuaina faʻalauteleina ma neurotrophic mole valaʻauina J147. Faʻataʻitaʻiga amioga faʻapitoa, talaʻaga, ELISA ma Western blotting na faʻaaogaina e suʻesuʻe ai le aʻafiaga o le J147 i mea e manatua ai, amyloid metabolism ma auala neuroprotective. Na suʻesuʻeina foi le J147 ile faʻataʻitaʻiga ole faʻaleagaina ole manatuaina ole iole C57Bl / 6J ma faʻatusatusa ile donepezil. Faʻamatalaga i luga o le falemaʻi ma le saogalemu o J147 o loʻo iai foʻi.
TULAFONO: Faʻamatalaga tuʻuina atu iinei faʻaalia ai o le J147 ei ai le mafai e laveaʻi ai faʻaletonu le mafaufau pe a faʻatautaia i se taimi mulimuli i le faʻamaʻi. O le agavaʻa o le J147 e faʻaleleia atili le manatuaina o iole matutua o le AD e faʻafesoʻotaʻiina ma lona faʻatumuina o le neurotrophic vala NGF (neula tuputupu aʻe vaega) ma BDNF (faiaʻoga maua neurotrophic vaega) faʻapea foʻi ma le tele BDNF-tali faʻamalosia polotini e taua mo le aʻoaʻo ma manatua. O le faʻatusatusaga i le va o le J147 ma le donepezil i le faʻataʻitaʻiga o le scopolamine na faʻaalia ai, e ui e tutusa uma vaega e lua i le laveaʻiina mai o ni mea e manatua ai i se taimi puʻupuʻu, ae o le J147 na sili atu i le laveaʻiina mai o le spatial memory ma le tuʻufaʻatasia o mea e lua na sili ona aoga mo faʻamatalaga ma manatu faʻaaoga.
Faaiuga ile J-147 mo le AD
O le J147 o se mea fou e fiafia i ai, e matua malosi lava, saogalemu i suʻesuʻega o manu ma gaioiga tuugutu. J147 o se ono AD togafitiga ona o lona mafai ona saunia vave aoga faʻapitoa, ma e i ai foi le ono mafai ona taofi ma atonu toe fesuiaʻi faʻamaʻi alualu i luma i faʻailoga meaola pei ona faʻaalia i nei suʻesuʻega.
J-147 Togafitiga Faʻafitauli o le Matua
J-147 ma Aneti-matua: Talaʻaga
O isumu na togafitia ma le J147 na sili atu le manatuaina ma le malamalama lelei, faʻamalologa o le toto i le faiʻai ma isi faʻalelei tino.
"I le amataga lava, o le unaʻiga o le faʻataʻitaʻia lea o fualaʻau i totonu o se ata fou o manu e tai tutusa lava ma le 99% o mataupu a Alzheimer," o le tala lea a Antonio Currais, o se sui o le Polofesa David Schubert's Cellular Neurobiology Laboratory i Salk. "Matou te leʻi vavalo o le a matou vaʻaia lenei ituaiga anti-matua aoga, ae J147 faia tuai isumu foliga pei o latou talavou, faʻavae i luga o le numera o physiological faataatiaga. " "E ui o le tele o vailaʻau na atiaʻe i le 20 tausaga ua tuanaʻi o loʻo faʻatutuina le teuina o le sela ile amyloid i le faiʻai (o se faʻailoga iloga lea o le faʻamaʻi), e leai se mea na faʻamaonia le aoga i le falemaʻi," o le tala lea a Schubert.
I ni tausaga ua tuanaʻi, na amata ai ona faʻalatalata Schubert ma ana paʻaga ile togafitia o le faʻamaʻi mai se itu fou. Nai lo le faʻatutuina o le amyloid, na filifili le falefaigaluega e leai i totonu le sili lamatiaga mafuaʻaga mo le faʻamaʻi - matua. Faʻaaogaina sela-faavae vaʻavaʻaiga faʻasolo agaʻi i le faiʻai poʻapo, na latou gaosia J147.
I le taimi ua tuanaʻi, na maua e le 'au e mafai e le J147 ona puipuia ma toe faʻafoʻi foʻi le manatuaina o mafaufauga ma faʻafitauli o le Alzheimer i isumu o loʻo iai se faʻamatalaga o le tofi faʻavae o le Alzheimer, o le ituaiga o isumu e masani ona faʻaaogaina. Peitai, o lenei ituaiga o faʻamaʻi aofia ai na o le 1% o Alzheimer mataupu. Mo isi uma, o le matua o le mafuaʻaga autu lamatiaga, fai mai Schubert. O le 'au na manaʻo e suʻesuʻeina aʻafiaga o le sui tauva i fualaʻau i luga o se ituaiga o isumu lena tausaga vave ma maua se faʻamatalaga o le le mafaufau e sili atu ona pei o le tausaga-fesoʻotaʻi tagata faʻafitauli.
J-147 ma Aneti-soifua matua: Faʻataʻitaʻiga derivation auiliiliga i Isumu
I lenei galuega lata mai, na faʻaaoga ai e le au suʻesuʻe se vaega tele o suʻesuʻega e fua ai le faʻaaliga o genes uma i le faiʻai, faʻapea foi ma le sili atu i le 500 tamaʻi siʻosiʻomaga o loʻo aʻafia ma le metabolism i faiʻai ma le toto o vaega e tolu o le vave o le matua o isumu. O vaega e tolu o vave televave isumu aofia ai tasi seti na talavou, tasi seti na tuai ma tasi seti na tuai ae fafagaina J147 ao latou matutua.
O isumu tuai na mauaina le J147 na faʻamalieina lona manatuaina ma isi suʻega mo le faʻamalamalamaina ma faʻaalia ai foi le sili atu ona faʻaaogaina o taʻavale. O isumu na togafitia ma le J147 sa i ai foʻi ni faʻailoga faʻapitoa o le Alzheimer i o latou faiʻai. O le mea taua, talu ai le tele o faʻamaumauga na aoina i luga o le tolu vaega o isumu, na mafai ai ona faʻaalia o le tele o vaega o le faʻaali o le kenera ma le faʻamalosia o metotia i isumu tuai na fafagaina J147 e tali tutusa lava ma tamaʻi manu. Na aofia ai faʻailoga mo le faʻateleina o le malosi o le tino, faʻaitiitia le mumu o le faiʻai ma faʻaititia le maualuga o le oxidized fatty acid i le faiʻai.
O le isi taua iloga o le J147 na puipuia le faʻasusu o le toto mai i microvessels i faiʻai o isumu tuai. Na taʻua e Currais: "O alatoto ua faaleagaina o se vaega masani lea o le matua o le soifua, ma i Alzheimer, e sili atu ona leaga."
AASraw o le tagata poto faapitoa gaosi oloa o Curcumin Derivative J-147.
Faʻamolemole kiliki ii mo upusii faʻamatalaga:
Faʻafesoʻotaʻi matou
Faaiuga ile J-147 mo le faʻafitauli tuai
O isumu na fafagaina le J147 na faʻateleina le malosi o le tino ma faʻaititia le mumu o faiʻai. Na maua e le au suʻesuʻe, o se sui tauva faʻataʻitaʻi faʻataʻitaʻi e teteʻe i le gasegase o le Alzheimer, e faʻaigoa o le J147, e tele mea e leʻi mafaufauina. anti-matutua aafiaga i manu.
O le 'au mai le Salk Institute na faʻaalia o le sui tau fualaʻau na galue lelei i se faʻataʻitaʻi o le matua e le masani ona faʻaaogaina i suesuega a Alzheimer. Ina ua togafitia nei isumu ma le J147, na sili atu lo latou manatuaina ma le malamalama lelei, o alualu toto maloloina i le faiʻai ma isi faʻalelei foliga tino.
J-147 Togafitiga Sili faʻafitauli o le mafaufau (MDD)
J-147 ma MDD: Talaʻaga
Tele maʻi le faʻavaivai (MDD) o se faʻamai ogaoga le mafaufau e fesoʻotaʻi ma le le lava o monoamine neurotransmitters, ae maise lava i mea e le masani ai o le 5-HT (5-hydroxytr Egyptamine, serotonin) ma ona faʻaola. O la matou suʻesuʻega talu ai na fautuaina ai le ogaoga o togafitiga ma se tusi curcumin mafua mai J147 faʻaalia antidepressant-pei aʻafiaga e ala i le faʻateleina faiaʻoga maua neurotrophic vaega (BDNF) tulaga i le hippocampus o isumu. O le suʻesuʻega na faʻalauteleina i luga o matou sailiga muamua ma suʻesuʻeina le antidepressant-pei aʻafiaga o togafitiga laʻititi o le J147 mo le 3 aso i tama ICR isumu ma lona ono talafeagai i 5-HT1A ma 5-HT1B talimalo ma lalo CAMP-BDNF faʻailoga.
J-147 ma MDD: Suʻega faʻataʻitaʻiga faʻataʻitaʻiga i isumu
Metotia: J147 i tui o le 1, 3, ma le 9 mg / kg (e ala i le gavage) na faia mo le 3 aso, ma o le anti-immobility taimi i le faʻamalosiʻau aau ma siʻusiʻu taofi faʻataʻitaʻiga (FST ma TST) na tusia. O le radioligand fusifusia faʻataʻitaʻiga na faʻaaogaina e fuafua ai le vavalalata o le J147 i le 5-HT1A ma le 5-HT1B taliga. E le gata i lea, na faʻaaoga le 5-HT1A poʻo le 5-HT1B agonist poʻo lona antagonist e fuafua ai poʻo fea 5-HT receptor subtype o loʻo aʻafia i le antidepressant-like effects o le J147. O fualaʻau faʻailo i lalo e pei o le CAMP, PKA, pCREB, ma le BDNF na fuaina foi e fuafua ai le faiga o gaioiga.
Tali: O iʻuga na faʻaalia ai o togafitiga laʻititi o le J147 na matua faʻaititia ai lava le taimi le gaioi uma i le FST ma le TST i se auala faʻalagolago i le vailaʻau. O le J147 na faʻaalia le maualuga vavalalata i vitro i le 5-HT1A receptor na saunia mai mice cortical tissue ma sa laʻititi malosi i le 5-HT1B receptor. O nei aʻafiaga o le J147 na poloka e le faʻataʻitaʻiga ma le 5-HT1A antagonist NAD-299 ma faʻaleleia e le 5-HT1A agonist 8-OH-DPAT. Ae ui i lea, o le 5-HT1B receptor antagonist NAS-181 e leʻi talisapaia faʻafitauli o le J147 i amioga faʻanoanoa. E le gata i lea, o le faʻataʻitaʻiga ma le NAD-299 na poloka ai le J147-faʻaosoina faʻaopoopoga i le cAMP, PKA, pCREB, ma le BDNF faʻaaliga i le hippocampus, ae o le 8-OH-DPAT na faʻaleleia atili ai aʻafiaga o le J147 i nei polotini.
Faaiuga i le J-147 mo Major depressive maʻi (MDD)
O iʻuga e taʻu mai ai o le J147 e faʻaosoina vave antidepressant-pei aʻafiaga i le vaitaimi o le 3-aso togafitiga e aunoa ma le faʻamalosia o le faʻatagaina o vailaʻau. O nei aʻafiaga ono faʻafesoʻotaʻia e le 5-HT1A-faʻamoemoeina cAMP / PKA / pCREB / BDNF signaling.
Sili atu Suesuega E uiga i le J-147
※ T-006: Faʻafefea Ona Faʻaleleia Lenei Suiga I le J-147
※ J147 o le phenyl hydrazide e maua mai i le natural compound curcumin.
※ J147 ei ai le 'afa-ola o le 2.5 itula i le faiʻai, 1.5 itula i le plasma, 4.5min i tagata microsome, ma le <4min i isumu microsome.
※ Faʻataʻitaʻi togafitiga masani ma le J147 puipuia le sciatic neura mai le alualu i luma o le maʻisuka-faʻasolosolo lemu o le tele myelinated alava conduction saoasaoa ae tasi tui o J147 vave ma faʻasolosolo fesuiaʻi faʻatutuina-faʻatupuina allodynia.
※ J147 togafitiga lalo-faʻatonutonuina BACE, faʻapea ona faʻateleina le APP (le lelei APP cleavage mulimuli ane faʻatupuina A to).
※ O le mitochondrial α-F1 subunit o ATP synthase (ATP5A) o se maualuga maualuga vavalalata faʻatulagaina o le J147, o se polotini na suesueina muamua i le tulaga o le matua ... o fualaʻau faʻalagolago taofiofia ATP5a.
※ J147 toe faʻaleleia tulaga o le acylcarnitines o loʻo faʻailoa mai ai se iuga lelei i mitochondrial dynamics.
'I NMDA talimalo, T-006 taofia ai le ova Ca2 + faatosina.
※ T-006 o loʻo i ai le puipuiga i lenei faiga e ala i le taofia uma o le auala MAPK / ERK ma le toe faʻaleleia o le auala PI3-K / Akt.
※ O isi mea e maua e pei o le 3j (dicyanovinyl-substituted J147 analogue) e mafai ona taofia ai le oligomerization ma le fibrillation o le β-amyloid peptides ma puipuia ai neura sela mai le β-amyloid-induced cytotoxicity.
O Fea e Faʻatau ai le J-147 Powder?
O le tulaga faʻatulafonoina o lenei nootropic o loʻo avea pea ma ponaivi o finauga ae o le a le faʻasaina ai oe mai le mauaina o oloa talafeagai. I tua atu i na mea uma, J-147 Alzheimer's clinical trial o loʻo amataina. E mafai ona e faʻatau le pauta i faleoloa i luga ole laiga a o e mauaina le faʻamanuiaga e faʻatusatusa ai le J-147 tau i tagata faʻatau eseese. Ae peitaʻi, e tatau ona e mautinoa e te faʻatau faleoloa mai i kamupani sapalai talafeagai ma suʻesuʻega tutoʻatasi a le fale suesue.
A e manaʻo i nisi J-147 mo le faʻatau atu, siaki totonu ma la matou faleoloa. Matou te sapalaiina le tele o nootropics i lalo o le lelei faʻatonutonu. E mafai ona e faʻatau tele pe faia faʻatau e tasi faʻamoemoeina i lau sikuriniutiki sini. Manatua lena, J-147 tau e faʻauo pe a faʻatau i le tele o aofaʻi.
AASraw o le tagata poto faapitoa gaosi oloa o Curcumin Derivative J-147.
Faʻamolemole kiliki ii mo upusii faʻamatalaga:
Faʻafesoʻotaʻi matou
AASraw o le faʻapolofesa faʻapolofesa o le J-147 paʻu o loʻo i ai le fale faigaluega tutoʻatasi ma le fale gaosi oloa tele e fai ma lagolago, o gaosiga uma o le a faia i lalo ole tulafono faatonutonu a le CGMP ma le faʻatonutonuina o le faʻaleleia lelei. O loʻo faʻamautu le faʻaogaina o le faʻaogaina, o faʻatauga faʻatau ma faʻatau siʻosiʻomaga e talia. Faʻafeiloaʻi e aʻoaʻo nisi faʻamatalaga e uiga i le AASraw!
Aapa mai ia te a'u neiTusitala o lenei tusiga:
Dr. Monique Na faauu Hong mai le UK Imperial College London Faculty of Medicine
Tusitala Fa'asaienisi Tusitala:
Cellular Neurobiology Laboratory, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Rd., La Jolla, CA 92037, ISA
2.Xiaoyu Pan
Matagaluega o Falema'i Falema'i ma Falema'i, Le Falema'i Fa'atasi Lona Lua ma le Falema'i Tamaiti a Yuying o Wenzhou Medical University, Wenzhou, Saina.
Iunivesite o Groningen, Netherlands.
Matagaluega o Bioscience ma Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 143-701, Korea.
5.Min Wang
Matagaluega o Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, ISA.
Inisetiute Fai'ai, Aoga o Fale Talavai, Iunivesite Faafomai a Wenzhou, Wenzhou, 325035, Saina.
E leai se auala e fa'amaonia ai pe fa'atupuina e lenei foma'i/saienitisi le fa'atau, fa'atau, po'o le fa'aogaina o lenei oloa mo so'o se mafua'aga. Aasraw e leai se mafutaga poʻo se mafutaga, faʻaalia pe leai foi, ma lenei fomaʻi. O le faʻamoemoe o le taʻua o lenei fomaʻi o le faʻaalia, faʻaalia ma faʻafetai i le maeʻa o suʻesuʻega ma atinaʻe galuega na faia e saienitisi o loʻo galulue i lenei vailaʻau.