Publication: Hiperkolesterolemi ve alzheimer arasındaki ilişkinin moleküler mekanizmasının ve vitamin E’nin rolünün incelenmesi
Abstract
HPERKOLESTEROLEM VE ALZHEIMER ARASINDAK LSKNN MOLEKÜLER MEKANZMASININ VE VTAMN E’NN ROLÜNÜN NCELENMES Nurgül Aytan ÖZET Alzheimer hastalıgı senil plaklarda A peptit birikimleri, nörofibriller yumaklarda asırı fosforile tau proteininin bölgesel birikimi sonucu olusan protein yıgılmaları ve oksidatif olarak hasarlı proteinlerin yıkımından sorumlu ubikitin-proteozom sistemin fonksiyon bozuklugu ile karakterize edilmektedir. Beyinde proteinlerin oksidatif olarak degisimine ve asırı lipit peroksidasyonuna neden olan serbest radikallerin artması ve Alzheimer hastalıgının patolojisinde oksidatif stresin önemi ile uyumlu pekçok çalısma bulunmaktadır. Son yıllardaki deneysel çalısmalar bir oksidatif stres kaynagının örnegin yüksek kolesterol gibi, A olusumunu baslatabilecegini ve kolesterolün kendisinin de Alzheimer hastalıgında diger bir güçlü oksidatif stres kaynagı oldugunu ileri sürmektedir. Vitamin E’nin oksidatif stresle baglantılı olan nörodejeneratif hastalıkları geciktirebilecegi veya önleyebilecegi ileri sürülmektedir. Bu çalısmanın amacı Alzheimer hastalıgı ve hiperkolesterolemi arasındaki iliskinin in vivo moleküler mekanizmalarının ve vitamin E’nin rolünün incelenmesidir. Hiperkolesterolemi ile indüklenen aterosklerotik tavsan modelinde beyinde 4 hafta süre sonunda % 2 kolesterol içeren diyetin Alzheimer hastalıgında tespit edilen nörofibriller yumaklar, tau hiperfosforilasyonu, protein karbonilasyonu ve proteozom fonksiyonu üzerine etkisi ve bu süreçte vitamin E’nin etkisi incelenmistir. Çalısmamız hiperkolesteroleminin lipit peroksidasyonu ve protein karbonilasyonunu arttırdıgını, bu artısın beyinde Alzheimer hastalıgında görülen benzer degisimlere neden olabilecegini ve vitamin E’nin bu süreçte koruyucu etkisi olabilecegini göstermektedir. perkolesterolemi, Alzheimer hastalıgı, Oksidatif stres, Vitamin E MOLECULAR MECHANISMS OF THE RELATION BETWEEN HYPERCHOLESTEROLEMIA AND ALZHEIMER’S DISEASE AND THE ROLE OF VITAMIN E Nurgül Aytan
Alzheimer’s disease (AD) is characterized by the accumulation of amyloid- (A) peptides in senile plaques and protein aggregates with regional accumulation of hyperphosphorylated tau in neurofibrillary tangles and a dysfunction of the ubiquitinproteasome system which degrades oxidatively damaged proteins. There is considerable evidence consistent with the importance of oxidative stress in the pathology of AD and the accumulation of free radicals, leading to excessive lipid peroxidation, oxidative modification of proteins in the brain. Current experimental evidence suggests that an initial source of oxidative stress, such as high cholesterol, may initiate amyloid- formation; which by itself is another potent source of oxidative stress in AD. It has been suggested that vitamin E may prevent or delay neurodegenerative disease associated with oxidative stress. The aim of this work is to investigate in vivo molecular mechanisms of the relation between hypercholesterolemia and Alzheimer’s disease and the role of vitamin E. In the present study, we have examined the effect of 2 % cholesterol-enriched diet for 4 weeks on brain proteasome function and protein carbonylation, tau hyperphosphorylation, neurofibrillary tangle formation which are detected in AD brain in the hypercholesterolemic rabbit model of atherosclerosis and the role of vitamin E in these processes. Our studies suggest that hypercholesterolemia increases lipid peroxidation and protein carbonylation and this might cause AD similar changes in the brain. Vitamin E may have a protective effect in this process. Hypercholesterolemia, Alzheimer’s disease, Oxidative stress, Vitamin E
Alzheimer’s disease (AD) is characterized by the accumulation of amyloid- (A) peptides in senile plaques and protein aggregates with regional accumulation of hyperphosphorylated tau in neurofibrillary tangles and a dysfunction of the ubiquitinproteasome system which degrades oxidatively damaged proteins. There is considerable evidence consistent with the importance of oxidative stress in the pathology of AD and the accumulation of free radicals, leading to excessive lipid peroxidation, oxidative modification of proteins in the brain. Current experimental evidence suggests that an initial source of oxidative stress, such as high cholesterol, may initiate amyloid- formation; which by itself is another potent source of oxidative stress in AD. It has been suggested that vitamin E may prevent or delay neurodegenerative disease associated with oxidative stress. The aim of this work is to investigate in vivo molecular mechanisms of the relation between hypercholesterolemia and Alzheimer’s disease and the role of vitamin E. In the present study, we have examined the effect of 2 % cholesterol-enriched diet for 4 weeks on brain proteasome function and protein carbonylation, tau hyperphosphorylation, neurofibrillary tangle formation which are detected in AD brain in the hypercholesterolemic rabbit model of atherosclerosis and the role of vitamin E in these processes. Our studies suggest that hypercholesterolemia increases lipid peroxidation and protein carbonylation and this might cause AD similar changes in the brain. Vitamin E may have a protective effect in this process. Hypercholesterolemia, Alzheimer’s disease, Oxidative stress, Vitamin E