Nā lāʻau lapaʻau o Alzheimer (AD drug) nā moho: J147, CMS121, CAD31
1. He aha ka Alzheimer's and Geroprotectors (GNPs)
ʻO Alzheimer ke kumu maʻamau o ka dementia, kahi ʻano dementia e kumu ai nā pilikia me ka hoʻomanaʻo, ka noʻonoʻo a me ka lawena. Hoʻonui mālie nā ʻōuli a hele a ʻoi aku ka maikaʻi ma mua o ka manawa, e lilo ana i mea koʻikoʻi e hoʻopilikia i nā hana o kēlā me kēia lā.Alzheimer ka maʻi nā kālā no ka 60 pakeneka i ka 80 pakeneka o nā hihia dementia. ʻO kaʻelemakule ka hopena nui loa no nā maʻi he nui, e like me ka maʻi Alzheimer (AD) a me ke kanulau.
( 9 21 13 )↗
PubMed Central
Ua mahalo nui ʻia mai ka National Institutes of HealthE hele i ke kumu
2. Ke kumu o ka maʻi o Alzheimer
Manaʻo nā kānaka noiʻi ʻaʻole hoʻokahi kumu o ka maʻi Alzheimer. Pehea ʻoe e loaʻa ai i ka maʻi ʻo Alzheimer? Hoʻolālā paha ka maʻi mai nā kumu he nui, e like me nā genetics, ka nohona a me ke kaiapuni. Ua ʻike nā ʻepekema i nā mea e hoʻonui ai i ka makaʻu o Alzheimer. ʻOiai kekahi mau kumu pilikia - ka makahiki, ka moʻolelo o ka ʻohana a me ka hoʻoilina - ʻaʻole hiki ke loli, hōʻike ʻia nā hōʻike e ʻike ʻia aia paha kekahi mau kumu ʻē aʻe i hiki iā mākou ke hoʻohuli.
-Awa
ʻO ka mea makaʻu nui ʻike ʻia no ka Alzheimer ke hoʻonui nei i ka makahiki, akā ʻaʻole ʻo Alzheimer kahi ʻāpana maʻamau o ka ʻelemakule. ʻOiai hoʻonui ka makahiki i ka makaʻu, ʻaʻole ia he kumu pololei o Alzheimer.
ʻO ka hapa nui o nā kānaka me ka maʻi he 65 a ʻoi. Ma hope o ka makahiki 65, hiki i ka pilikia o ka pālua o Alzheimer i kēlā me kēia ʻelima mau makahiki. Ma hope o ka makahiki 85, hiki ka ʻino i kahi hapakolu.
-Kaukala moʻolelo
ʻO kekahi kumu pilikia nui ka moʻolelo o kaʻohana. ʻO ka poʻe i loaʻa i ka makua, ke kaikuaʻana, aʻo ke kaikuahine paha me Alzheimer,ʻoi aku ka mea i loaʻa i kēia maʻi. Hoʻonui ke kuhi inā nui ka maʻi o hoʻokahi o kaʻohana o kaʻohana.
-Genetics (heredity)
Uaʻike nā kānakaʻepekema he pilina ka'ā'ī ma Alzheimer. ʻEluaʻano o nāʻanoʻano e pili ana i ke kuʻiʻana o kekahi kanaka i kahi maʻi: nā kēneʻokoʻa a me nā genes deterministic.
Kaʻinoʻino
Aia kahi loulou ma waena o ka poʻo ʻeha a me ka hopena o ka dementia e hiki mai ana. Palekana i kou lolo ma ke kāʻei ʻana i kou kāʻei noho, ka hoʻokomo ʻana i kou mahiole i ke komo ʻana i nā haʻuki, a "hāʻule-hōʻoia" i kou home.
ʻO ke poʻo o ke poʻo
( 12 24 23 )↗
PubMed Central
Ua mahalo nui ʻia mai ka National Institutes of HealthE hele i ke kumu
3. ʻO nā moho lāʻau lapaʻau a Alzheimer (AD drug): J147, CMS121, CAD31
I kēia lā, ʻo Alzheimer ka mua o ka noiʻi biomedical. Ke hana nei nā mea noiʻi e wehe i nā ʻano o ka maʻi o Alzheimer a me nā dementias ʻē aʻe i hiki. ʻO kekahi o ka holomua nui loa i hoʻomālamalama i ka hopena o Alzheimer i ka lolo. ʻO ka manaʻolana kēia ʻike maikaʻi aʻe e alakaʻi i nā lāʻau hou. Ke hoʻokolokolo ʻia nei nā ʻano hiki i kēia manawa a puni ka honua.
ʻO ka 2,4-Dinitrophenol (DNP) lāʻau paʻakikī maikaʻi loa i loko o bodybuilding
Ua hoʻomaka ka papahana neurobiologyʻo Salk me nā kinikonaʻelua i loaʻa i loko o nā mea kanu i hōʻike i nā mea lapaʻau: iʻa, kahi hua maoli i huaʻia mai nā hua a me nā huaʻai, a me curcumin, mai ka'āpana kukui. Mai kēia mau mea, ua hui pūʻia ka huiʻekolu AD lāʻau lāʻau ʻo nā moho e pili ana i ko lākou hiki ke pale i nā neurones mai nā maʻi he nui e pili ana i ka loloʻelemakule. Ua hōʻike ka hana i kēia mau mea kohoʻekolu (ʻikeʻiaʻo CMS121, CAD31 a me J147), a me ka iʻa a me curcumin, hoʻemiʻia nā'ōmumu mole o kaʻelemakule, a me ka dementia, a hoʻonui i ka laulā o waena o nāʻiole a me nā nalo.
ʻO ka mea nui, ua hōʻikeʻia e ka huiʻo nā alapili'ulaʻi e hanaʻia e kēia mau mea noiʻi lāʻau maʻamau e like like meʻelua mau pūnaehana hōʻano houʻia iʻikeʻia e hoʻonui i ke ola o nā holoholona he nui. No kēia kumu, a ma muli o ka hopena o kā lākou aʻo muaʻana, ua'ōlelo ka hui i ka iʻa, curcumin a meʻekolu mau mea noiʻi lāʻau maʻamau a pau e pili ana i keʻano o ka geroneuroprotectors.
ʻO nā haʻawina'ē aʻe i loko o ka laikini e hoʻoholo ana inā he hopena kēia mau mea ma nāʻano o waho ma ka lolo. "Inā loaʻa kēia mau lāʻau lapaʻau no nā'ōnaehana'ē aʻe, e like me ka mālamaʻana i ka hana'ōkiko a me ka olakino olakino, hiki ke hoʻohanaʻia i nā ala'ē aʻe e mālama ai a paleʻana i nā maʻi o kaʻelemakule," e'ōlelo anaʻo Schubert.
- ʻO nā moho Alzheimer (drug AD) moho: J147
Curcumin, ka mea nui o ka turmeric spry Indian, he hui multitarget ia e hoʻemi ana i ka hoʻolālā, ka hana ROS, ka'awaʻahu amyloid, a me ka excitotoxicity, a he kūpono loa ma nāʻano o ke kola o AD. Eia naʻe,ʻo ka curcumin ka hana haʻahaʻa liʻiliʻi loa, ka maikaʻiʻole o ka biovavailability, a me ka lolo o ka lolo. No ka hoʻomaikaʻiʻana i ka hana neurotropic a me ka paʻa o ka holomua o ka curcumin, ua hoʻohana mākou i ka hoʻomehana hoʻoikaikaʻike SAR no ka hoʻomaikaʻiʻana i nā mea pharmacological ma ka manawa hoʻokahi e hoʻonui i kona ikaika a me nāʻano o kāna mau hana ola. I ka hoʻomaka mua, ua hoʻololiʻia keʻano o ka'āpana o ka curgone a me ka pyrazole e hana i ka CNB-001, me ka hoʻonuiʻana i ke kūlana a me ka neuroprotectiveʻoihana ma luna o ka curcumin. Uaʻikeʻia nā'ōnaehana o nā hui maʻekolu o nā'āpana phenyl o CNB-001 e ponoʻole nā hui hydroxl no kaʻoihana i nā hananaʻikeʻehiku. ʻO ka hoʻohuiʻana oʻelua mau methyl i ka pyrazole i hoʻohuiʻia me ka pyrazole i alakaʻiʻia i CNB-023 me ka manaʻoi aʻe ma luna o CNB-001. Eia nō naʻe,ʻo CNB-023 he lipophilic kiʻekiʻe (cLogP = 7.66), a he mau pūʻona me ka lipophilicity kiʻekiʻe. No ka hoʻohaʻahaʻaʻana i ka lipophilicity a ho'ākāka i nā kumumalima o nā koi no kaʻoihana, ua weheʻia kekahi o nā hui cinnamylʻelua a uaʻoi aku ka hoʻonuiʻana i ka hoʻomanaʻoʻana i kahi mole mole nui loa. J147. ʻO J147 ka 5-10 manawa iʻoi aku kaʻoi aku o ka pahuhopu i nā koi a pau loa e like me CNB-001, oiai he nui aʻoiʻole ka hana o curcumin i kekahi hopena. ʻAʻoleʻo J147 wale nō ka mana loa akā he maikaʻi nāʻano physicchemical (MW = 350, cLogP = 4.5, tPSA = 42). J147 (1146963-51-0) ua aʻo nuiʻia i nā hiʻona maʻamau a me nā hiʻohiʻona AD i kahi o kona kūlana maikaʻi loa.
ʻO ka hopohopo e hana i ka J147 hiki ke hoʻohaʻahaʻa ʻia i nā amine / hydrazine ʻaʻala e hiki ke carcinogenic. No ka ʻimi ʻana i kēia hiki, ua hoʻopaʻa ʻia ke kūpaʻa metabolic o J147 i nā microsome, i ka plasma mouse, a me vivo. Ua hōʻike ʻia kēlā J147 (1146963-51-0)ʻaʻole i hoʻohaʻahaʻaʻia i nā amine a me nā hydrazines, ua kūpaʻa loa ka scaffol, a ua hoʻololiʻia iʻelua aʻekolu paha metabolites i loko o ke kanaka, kaʻiole, ka iole, ka'īlio a me ka'īlio'īlio microsomes. No ka nānāʻana i ka palekana o kēia mau melikapila, ua hōʻano'ē mākou i nā'ōhua likeʻole microsomal metabolites a me ka ho'āʻoʻana iā lākou no ka hana ola kino i nā manaʻo neuroprotection. ʻAʻohe o kēia mau metabolites iʻawaʻawa, a he nui nā mea metabolites e hana likeʻole me ka mea o J147.
- Nā moho Alzheimer (lāʻau AD) nā moho: CMS121
ʻO CMS121 ka hopena o ka iʻa. I nā makahiki i hala aku nei, ua hōʻike mākou i ka flavonoid fisetin kahi hana waha, neuroprotective, a me ka mole hoʻomaikaʻi i ke ʻano i nā ʻano holoholona o nā maʻi CNS. ʻO Fisetin kahi hana antioxidant pololei a hiki ke mālama i nā pae intracellular o GSH ma lalo o ke koʻikoʻi. Hoʻohui ʻia, loaʻa i ka fisetin nā hana neurotrophic a me anti-inflammatory. Hōʻike kēia ākea ākea o nā hana i ka fisetin i ka hiki ke hōʻemi i ka nalo ʻana o ka hana neurological e pili ana i nā maʻi he nui. Eia nō naʻe, ʻo kona EC50 kiʻekiʻe loa i nā hoʻokolohua e pili ana i ka cell (2-5 μM), low lipophilicity (cLogP 1.24), tPSA kiʻekiʻe (107), a me bioavailability maikaʻi ʻole i kaupalena ʻia ka fisetin no ka hoʻomohala hou aʻe ma ke ʻano he moho lāʻau.
ʻO ka pahuhopu ka hoʻomaikaʻi ʻana i ka ikaika o ka fisetin ma nā ala neuroprotective he nui a i ka manawa like e hoʻololi ana i kāna mau waiwai physicochemical e kūlike me nā lāʻau CNS kūleʻa (kaumaha mole ≤ 400, cLogP ≤ 5, tPSA ≤ 90, HBD ≤ 3, HBA ≤ 7) .Elua mau ʻano ʻokoʻa i hoʻohana ʻia e hoʻomaikaʻi i ka fisetin. I ka mua, ua hoʻololi ʻia nā hui hydroxyl ʻokoʻa i kahi ʻano ʻōnaehana e hoʻopau ai i nā metabolite sulfate / glucuronidate hiki. I ka lua o ka hoʻokokoke ʻana, ua hoʻololi ʻia ka scaffold flavone i kahi quinolin, ʻoiai e mālama ana i nā mea kūkulu kī nui o ka fisetin. I ka hoʻohana ʻana i kā mākou loaʻa ʻana i ka lāʻau multitarget, ua hana mākou i kekahi mau derivatives me nā hana i hoʻonui ʻia i ka neuroprotective oxytosis a i ʻO ka hoʻāʻo ʻana ischemia vitro. ʻEkolu mau hana hou o ka fisetin i mālama ʻia i nā derivatives, me ka mālama ʻana o GSH, ka pāpā ʻana o ka lipopolysaccharide (LPS) i hoʻoulu ʻia i ka microglial, a me ka hoʻokaʻawale ʻana o ka cell PC12, kahi ana o ka hana neurotrophic. ʻO ka flavone derivative CMS-140 a me ka quinolone derivative CMS-121 he 600 a he 400 mau manawa ka nui o ka mana, ma mua o ka fisetin i ka ischemia assay
- Nā moho Alzheimer (drug AD) moho: CAD31
ʻO nā maʻi a pau o ka CD31 maʻamau i loko o keʻano o ka paleʻana i kekahi o nā meaʻino i nā maʻi o nā neurodegenerative.
ʻO CAD31 kahi moho lāʻau ʻo Alzheimer (AD) i wae ʻia ma ke kumu o ka hiki ke hoʻoulu i ke kope ʻana o ke kanaka embryonic stem cell-i loaʻa i nā neural precursor cells e like me nā ʻiole APPswe / PS1ΔE9 AD. No ka neʻe ʻana iā CAD-31 i ke keʻena lāʻau, ua mālama ʻia nā hoʻokolohua e hoʻoholo ai i kāna mau waiwai neuroprotective a me nā lāʻau, a me ka hoʻowalewale ʻana i kāna pono therapeutic i kahi ʻano iole paʻakikī o AD.
( 16 34 25 )↗
PubMed Central
Ua mahalo nui ʻia mai ka National Institutes of HealthE hele i ke kumu
Kōkuʻu 4
Ke hoʻomau nei ka pūʻulu noiʻi i ka loaʻaʻana oʻelua GNP i loko o nā hoʻokolohua kino kanaka. ʻO ka'eneke iʻa, CMS121, aia i kēia manawa i kaʻike o nā mea lāʻau e pono ai ka palapala FDA e hoʻomaka i nā hoʻokolohua kino. ʻO ka curcumin derivative, J147, aia ma lalo o ka hōʻike FDA no ka haʻawina e hoʻomaka i nā hoʻokolohua clinical no AD i ka makahiki e hiki mai ana. Hoʻolālā ka pūʻulu e hoʻokomo i nā hōʻailona kino no kaʻelemakuleʻana i nā hoʻokolohuaʻokoʻa no ka hōʻailona no nā hopena o ke kumuhana kūpono. Ua'ōlelo nā mea noiʻi i kaʻikeʻiaʻana o kēia mau mea noiʻi lāʻau maʻamau e hōʻoia i ka hōʻailona maʻamau a lākou i hoʻolālā ai e like me keʻano o keʻano Pūnae GNP nā mea e kōkua i ka hoʻonuiʻana i ke olakino olakino. ʻO kēia ka mea hiki ke hoʻonui i ka pipeline no nā lāʻau lapaʻau e mālama ai i nā maʻi o kaʻelemakule no ka meaʻaʻohe manawa ola.
ʻO AASraw ka mea hana loea o J147, CMS121, CAD31 pauka nona ka lab kūʻokoʻa a me ka hale hana nui e like me ke kākoʻo, e hoʻokō ʻia nā hana āpau ma lalo o ke kānāwai CGMP a me ka ʻōnaehana mālama maikaʻi. Paʻa ka ʻōnaehana hoʻolako, ʻae ʻia nā kauoha kūʻai a me nā mea kūʻai nui. Welcome e aʻo hou i ka ʻike e pili ana iā AASraw!
E kiʻi mai iaʻu i kēia manawa