Poli(ADP-ribozil) polimeraza u životu i smrti živčanih stanica

undergraduate thesis

• Title (english): Poly(ADP-ribosyl) polymerase in life and death of neural cells
• Author: Josip Ahel
• Mentor: Maja Matulić (mentor)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2014, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Poli(ADP riboza) je post-translacijska modifikacija proteina koju iz NAD+ sintetiziraju proteini iz obitelji Poli(ADP-ribozil) polimeraza. Poli(ADP-ribozil)acija je reverzibilna reakcija te povratnu reakciju katalizira nekolicina specifičnih enzima. Poli(ADPribozil) acijski sustavi su prisutni u svim eukariotskim supergrupama. U ovom se radu nudi pregled dosadašnjih saznanja o ulogama poli(ADP-ribozil)acije u popravku DNA, reorganizaciji kromatina, regulaciji transkripcije te nekrozi i apoptozi, s posebnim osvrtom na učinke poli(ADP-ribozil)acije u živčanom sustavu. Poli(ADP-ribozil) polimeraze ključan su medijator u tim procesima regulirajući aktivnost čitavog niza proteina koji su direktno uključeni u spomenute procese i to stvaranjem skela poli(ADP riboze) ili direktnom modifikacijom ciljnih proteina. Nadalje, pretjerana aktivnosti poli(ADP-ribozil) polimeraza može dovesti do nekrotične smrti stanica uslije energetskog šoka ili parthanatosa uslijed translokacije mitohondrijskih signala smrti. Do pretjerane aktivacije poli(ADP-ribozil) polimeraza u živčanom sustavu može doći uslijed ekscitotoksičnog djelovanja glutamata te akutnih oboljenja poput moždanog udara i traumatskih ozljeda, kada dolazi do oksidativnog stresa, značajne aktivacije upalnih procesa te neurodegeneracije uz posredovanje poli(ADPribozil) polimeraze. Postoje indikacije da poli(ADP-ribozil) polimeraza ima ulogu u patologiji Parkinsonove i Alzheimerove bolesti. U svim spomenutim procesima bitnu ulogu vjerojatno također imaju i glikohidrolaza terminalne ADP riboze te poli(ADP-ribozil) glikohidrolaza, koje su puno slabije istražene, no učinak disfunkcije ovih proteina na živčani sustav naglašava njihovu važnu ulogu u istom.

Abstract (english)

Poly(ADP-ribose) is a post-translational modification of proteins synthesized by the poly(ADP-ribosyl) polimerase family enzymes from NAD+. Poly(ADP-ribosyl)ation is a reversible reaction with specific enzymes catalysing the hydrolysis of poly(ADP-ribose). Poly(ADP-ribosyl)ation systems are found in all six eukaryotic supergroups. In this paper, I offer a review of up-to-date findings about the roles of poly(ADP-ribosyl)ation in DNA repair, chromatin reoragnization, transcription regulation, necrosis and apoptosis, with emphasis on the function of poly(ADP-ribosyl)ation in the nervous system. In these processes, poly(ADP-ribosyl) polimerases play a key role regulating the activity of numerous proteins directly engaged in these processes. This is achieved by forming poly(ADP-ribose) scaffolds or by direct modification of target proteins. Moreover, excessive poly(ADP-ribosyl) polimerase activity may lead to necrotic cell death by energy shock or to parthanatos caused by translocation of mitochondrial death signals. In the nervous system, excessive poly(ADPribosyl) polimerase activity can be caused by the excitotoxic action of glutamate and by acute conditions, such as stroke and traumatic injuries, during which cells experience oxidative stress, significant activation of inflammatory processes and poly(ADP-ribosyl) polimerasemediated neurodegeneration. Poly(ADP-ribosyl) glycohydrolase and terminal (ADP-ribose) glycohydrolase most likely also play significant roles in the aforementioned processes as disfunctionality in these two proteins has severe neurodegenerative effects.

• Keywords: poli(ADP-ribozil); polimeraza
• Keywords (english): poly(ADP-ribose); polimerase
• Language: croatian
• URN:NBN: urn:nbn:hr:217:330498
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: undergraduate; Academic / professional title: sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije (sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-12-06 09:37:34