The neuroprotective effect of dehydroepiandrosterone-sulphate (DHEAS) in in vitro models of Alzheimer's disease

Alzheimerova bolest (AB) je najučestaliji oblik demencije koji se očituje kroz gubitak raznih kognitivnih sposobnosti. Uzrokovana je propadanjem neurona i sinaptičkih veza unutar mozga i visoko je povezana s nakupljanjem peptida amiloid beta (Aβ) u središnjem živčanom sustavu. Uglavnom se razvija kod ljudi starijih od 65 godina, a udio oboljelog stanovništva je u stalnom porastu. Bolest je posljedica velikog broja čimbenika, što je čini vrlo složenom i zasad neizlječivom. Istraživanja u biomedicini su, između ostalog, usmjerena i na pronalazak tretmana koji bi značajno usporili proces odumiranja neurona u mozgu. Potencijalan kandidat za to je neurosteroid dehidroepiandrosteron-sulfat (DHEAS) koji u središnjem živčanom sustavu pomaže u očuvanju neurona, a njegove endogene razine pozitivno koreliraju s kognitivnim sposobnostima. Cilj ovog rada bio je istražiti potencijalni učinak DHEAS-a u promociji preživljenja stanica korištenjem dvaju in vitro modela AB-a, primarne kulture mišjih neurona i stanične linije SH-SY5Y, tretiranih oligomerima Aβ. Rezultati istraživanja sugeriraju neuroprotektivno djelovanje DHEAS-a u staničnom modelu AB-a temeljenom na primarnoj kulturi mišjih neurona. S druge strane, isti učinak nije bilo moguće postići na staničnoj liniji SH-SY5Y tretiranoj oligomerima Aβ.Alzheimer's disease (AD) is the main cause of dementia which is characterised by the loss of various cognitive abilities. It is caused by neural and synaptic loss within the brain and is highly associated with the accumulation of amyloid beta (Aβ) peptide in the central nervous system. It mostly affects people older than 65 years and the overall percentage of people affected by it is constantly increasing. Many factors play a role in the formation of the disease, which makes it very complex and currently incurable. Research in biomedicine is, among other things, focused on finding treatments that would significantly reduce the neural loss in the brain. A potential candidate for this is the neurosteroid dehydroepiandrosterone-sulphate (DHEAS) which participates in neuronal preservation in the central nervous system, and its endogenous levels positively correlate with cognitive abilities. The aim of this research was to investigate the potential effect of DHEAS in promoting cell survival using two in vitro models of AD, primary cultures of mouse neurons and the SH-SY5Y cell line, both treated with Aβ oligomers. The obtained results suggest a neuroprotective effect of DHEAS in an in vitro model of AD based on the primary culture of mouse neurons. On the other hand, the same effect could not be achieved on the SH-SY5Y cell line treated with Aβ oligomers