Title Imunoterapijski pristupi liječenju Alzheimerove bolesti Title (english) IMMUNOTHERAPEUTIC APPROACHES FOR
ALZHEIMERS DISEASE Author Klara Krpina Mentor Ivana Munitić (mentor)Committee member Jelena Ban (predsjednik povjerenstva)Committee member Miranda Mladinić Pejatović (član povjerenstva)Committee member Ivana Munitić (član povjerenstva)Granter University of Rijeka Defense date and country 2018, Croatia Scientific / art field, BIOTECHNICAL SCIENCES Abstract Alzheimerova bolest (AB) je progresivna neurodegenerativna bolest koja kulminira teškom demencijom. Pod pojmom demencija se smatra gubitak kognitivnih sposobnosti koji je kroničan i ireverzibilan. Može se javiti u bilo kojoj dobi, ali uglavnom zahvaća starije. AB zahvaća oko 4% bolesnika u dobi od 65 do 74 godina te 30% onih iznad 85 godina. Pacijenti inicijalno imaju probleme s gubitkom kratkotrajne memorije, a zatim slijedi zbunjenost, agitacija, poremećaji u ponašanju te potpuni gubitak kognitivnih sposobnosti. AB je multifaktorijalna bolest, što znači da ima genetsku i okolišnu pozadinu. Bolest se javlja u dva oblika, nasljednom i sporadičnom, a sporadični oblik može također imati genetsku podlogu u svom razvoju. Mutacije u tri različita gena povezane su s obiteljskom poviješću bolesti: u genu koji kodira za amiloid-β prekursorski protein (APP), zatim u genu za PSEN1 (Presenilin 1) i genu za PSEN2 (Presenilin 2). Sporadični oblik, koji se još naziva i kasni oblik bolesti se javlja nakon 65. godine života te je najčešći oblik Alzheimerove bolesti. Polimorfizam gena za apolipoprotein E, potvrđen je kao rizični čimbenik. Patohistološko obilježje AB su pojava plakova amiloida-β (Aβ) i neurofibrilarnih čvorova u kojima se nakuplja fibrilarni protein Tau. Postoji nekoliko hipoteza o patologiji Alzheimerove bolesti. Sve više prihvaćen model za razvoj novih terapija je amiloidna hipoteza koja kaže da je odlaganje Aβ glavni uzrok Alzheimerove bolesti, nakon čega slijedi nakupljanje Tau kao izravna posljedica ove akumulacije. Ova hipoteza sugerira da terapije otklanjanja Aβ mogu biti korisne u liječenju Alzheimerove bolesti. Ovdje ću opisati četiri različita antitijela koja se ispituju i koja ciljaju Aβ. Također, ovaj rad opisuje protutijela koja ciljaju Tau, kao jedan od glavnih ciljeva terapije Alzheimerove bolesti. Nakon desetljeća istraživanja ove bolesti, lijek koji bi je izliječio i dalje ne postoji. Korištenje imunoterapije u Alzheimerovoj bolesti je izazvalo veliko zanimanje. Iako dosadašnji pokušaji još nisu bili toliko uspješni u
Comment [JB1]: Zar se ne podrazumijeva da nasljedni oblik bolesti ima genetsku podlogu? Možda bi logičnije bilo da se to kaže samo za sporadični oblik.
usporavanju napredovanja bolesti, uspjeli su značajno smanjiti nakupljanje Aβ. Sve u svemu čini se da je imunoterapija jedno od najvećih dostignuća u borbi protiv ove teške bolesti i niz pokušaja poboljšanja te terapije su u tijeku.
Abstract (english) Alzheimer's disease (AD) is a progressive neurodegenerative disease that culminates with severe dementia. Dementia is a loss of cognition and it is chronic and irreversible. It can occur at any age, but mostly affects the elderly. It affects approximately 4% of patients aged 65 to 74 and 30% of those older than 85 years. Patients initially have problems with the loss of short-term memory, followed by confusion, agitation, behavioral disorders, and severe loss of cognitive abilities. AD is a multifactorial disease, meaning that it has a genetic and environmental background. The disease occurs in two forms; familiar and sporadic, and sporadic form can also have a genetic basis in development. Mutations in three different genes are linked to the family history of the disease; mutations in the gene encoding the amyloid-β APP protein precursor, then mutations in PSEN1 gene (Presenilin 1) and gene for PSEN2 (Presenilin 2). The sporadic form, also known as the late form of the disease, occurs after age of 65 and is the most common form of Alzheimer's disease. Polymorphism of the Apolipoprotein E gene, was confirmed as a risk factor. Characteristic features of AD are the appearance of amyloid-β (Aβ) plaques and neurofibrillary tangles, made of fibrillar protein Tau. There are several hypotheses about the pathology of AD. More accepted model for development new therapies is the amyloid hypothesis that says that deposition of amyloid β protein (Aβ) is the main cause of
Comment [JB2]: Ako je niz pokušaja, onda je jednina.
Comment [JB3]: Ja bi sve stavila malim slovom
Alzheimer disease which is followed by the accrual of tangles as the direct consequence of this accumulation. This hypothesis strongly suggests that targeting Aβ could be beneficial for treatment of AD. Here I report four different antibodies that are being tested and which target Aβ. Also, this thesis describes antibodies that target Tau, as one of the main goals in immunotherapy of AD. After decades of investigating AD, no cure is currently available for this disease. The use of immunotherapy in AD has caught some serious attention. Although attempts that have been made so far have not yet been successful in changing the disease course, they were able to substantially diminish Aβ load. Overall, it seems that immunotherapy is one of the most promising achievements in the fight against this devastating disease and efforts to improve it are undergoing.
Keywords
Alzheimerova bolest
demencija
imunoterapija
Amiloidna hipoteza
Keywords (english)
Alzheimer’s disease
dementia
immunotherapy
amyloid hypothesis
Language croatian URN:NBN urn:nbn:hr:193:950198 Study programme Title: Biotechnology and drug research Type of resource Text File origin Born digital Access conditions Access restricted to students and staff of home institution Terms of use Created on 2018-10-26 07:29:32
