Nā lāʻau lapaʻau o Alzheimer (AD drug) nā moho: J147, CMS121, CAD31

Posted on 07/10/2022 by Kauka Monique kākauʻo ia i loko J147.

" ʻO ka maʻi o Alzheimer, ke kumu maʻamau o ka dementia, he ʻano dementia e hoʻopilikia ai i ka hoʻomanaʻo, ka noʻonoʻo, a me nā pilikia. 'O ka ma'i 'o Alzheimer ka 60% a hiki i ka 80% o ka ma'i dementia. A, no nā maʻi he nui, e like me ka maʻi Alzheimer (AD) a me ka maʻi kanesa, ʻo ka ʻelemakule ke kumu pilikia nui loa. "

1. He aha ka Alzheimer's and Geroprotectors (GNPs)
2. Ke kumu o ka maʻi o Alzheimer
3. ʻO nā moho lāʻau lapaʻau a Alzheimer (AD drug): J147, CMS121, CAD31
Kōkuʻu 4

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.

Geroprotectors, he senotherapeutic ka mea e pili i ka hopena o ke kumu o kaʻelemakule a me nā maʻi e pili ana i nā makahiki, a pēlā e hoʻolōʻihi ai i ke ola o nā holoholona. Uaʻikeʻia kahi noiʻi hou Salk i kahi papahana kūikawā o kēia mau pūnaewele, kahi i hoʻonohonohoʻia i nā geroneuroprotectors (GNPs), he mau mea noiʻi lāʻau noi a MS a hoʻolōʻihi i ka hanaʻelemakule ma kaʻohe.

( 9 21 13 )↗

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

ʻO kekahi o nā hōʻike ikaika loa e pili ana i ka lolo no ke olakino. He pilina kēia pili, no ka mea, hānaiʻia ka lolo e kekahi o nā pūnaeweleʻoi loa o ke koko, a he puʻuwai ka naʻau no ka pipiʻana i ke koko ma o kēia mau kīʻaha koko i ka lolo.

( 12 24 23 )↗

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 pahuhopuʻo ia e hoʻonui i ka mana o ka iʻa i nā alanui neuroprotective ma ka manawa like e hoʻololi ana i kona mau waiwai physicchemical i mea e kū like me nā mea i loaʻa i ka CNS mau lāʻau (kaumaha kaumaha kaumaha ≤ 400, cLogP ≤ 5, tPSA ≤ 90, HBD ≤ 3, HBA ≤ 7). Ua hoʻohanaʻia i kēia mauʻokoʻaʻelua e hoʻonui i ka iʻa. I ka mea mua, ua hoʻololiʻia nā hui hydroxl i nāʻano maʻamau no ka hoʻopauʻana i nā metabolites sulfate / glucuronidate. I ka lua o ka heleʻana, ua hoʻololiʻia ka flavone scaffol i quinoline, a ma ka manawa hoʻokahi e mālama nei i nāʻano kumu hana nui o ka iʻa. Ma muli o kaʻikeʻana i kā mākouʻikeʻike lāʻau lāʻau nui, ua hana mākou i kekahi mau hua'ōlelo me nā hana nui iʻoi aku i nā neuroprotective oxytosis a i nā kālepa ischemia vitro. ʻEkolu mau hana hou o ka iʻa i kāohiʻia i nā huahana, e like me ka mālamaʻana i ke GSH, ka hanaʻana o ka lipopolsaccharide bacteria (LPS) i hoʻokomoʻia ka hananaʻana o ka microgial, a me ka PC12 o kaʻokoʻaʻana o ka cell, kahi ana o nā hana neurotrophic. ʻO nā hua hoʻoheheʻeʻiaʻo CMS-140 a me quinolone CMS-121 ka 600 a me ka 400 manawaʻoi aʻe,ʻoi aʻe, ma mua o ka iʻa i ka hopena ischemia (Nānā, pēlā e hiki ai ke mālama i nāʻanoʻenehana o kahi polyphenol me ka hoʻomaikaʻiʻana i nā physiochemical and nāʻoihana pharmacological o ka pūpū.

- 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.

Hiki i nā CAD31 nā kūlana neuroprotective kaha i nāʻanoʻokoʻa pūpiliʻeono iʻikeʻia e pili ana i nā meaʻino iʻikeʻia ma ka lolo mua. Ke hōʻikeʻia e nā mea Pharmacological a me nā haʻawina o nā haʻawina huli haʻahaʻa i ka CAD31 i loko o ka lolo a me ka palekana. I ka hānaiʻana i kaʻelemakule, loaʻa nā APPswe / PS1ΔE9 AD i nā mice e hoʻomaka ana i nā makahiki 10 no ka 3 mau mahina'ē aʻe ma keʻano hōʻailona maʻi o ka maʻi, ua nui ka ho'ēmiʻana o ka pauʻole o ka hoʻomanaʻo a me ka umauma o ka lolo, a me ka hoʻonuiʻana i ka'ōlelo o nā pūnaepa synaptic. Uaʻikeʻia kaʻikeʻana i kaʻikepili me kaʻikeʻole i ka hopena o ka mea i loaʻa i ka lolo ma ka lolo a me ka plasma i ka hopena o CAD-31. Uaʻikeʻia kaʻikeʻana o CAD-31 i nā hopena nui ma ka hanaʻana i ka hala a me ke ala o ka ikaika.

( 16 34 25 )↗

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

Mea kākau o kēia ʻatikala:

Kauka Monique Ua puka 'o Hong mai ke Kula Nui o UK Imperial College London Faculty of Medicine

Mea kākau moʻolelo puke moʻolelo ʻepekema:

1. ʻO Chen-yi Cheng
Kula Lapaʻau Kumu, Xinxiang Medical University, Xinxiang, Henan 453003, Kina
2. Guoheng Zhong
Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, 510005, Kina
3. Hanika Rizo
Keʻena ʻepekema Honua, Ottawa-Carleton Geoscience Center, Carleton University, Ottawa, ON, K1S 5B6, Kanada
4. Bing Z. Carter PhD
Ke Kulanui o Texas MD Anderson Cancer Center, Dept of Leukemia, 1515 Holcombe Blvd, Houston, TX 77030, USA

5.Jeffrey A. Herron

Keʻena ʻOihana Kimia a me Biological, Ke Kulanui o Wisconsin-Madison, Madison, WI 53706, USA
ʻAʻole ʻae kēia kauka/ ʻepekema i ke kūʻai, kūʻai ʻana, a hoʻohana paha i kēia huahana no kekahi kumu. ʻAʻohe pili a pili ʻole ʻo Aasraw, i hōʻike ʻia a i ʻole, me kēia kauka. ʻO ke kumu o ka haʻi ʻana i kēia kauka, ʻo ia ka hoʻomaikaʻi, hoʻomaikaʻi a hoʻomaikaʻi i ka hana noiʻi a me ka hoʻomohala piha i hana ʻia e nā ʻepekema e hana nei i kēia mea.

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