Alp Yigit Ozdemir

Charles University, Czech Republic

Abstract Title: Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β42 (Aβ42) protein, forming toxic aggregates that damage neuronal cells. Various cell death pathways are linked to its activity, including apoptosis, necroptosis, pyroptosis, oxidative stress, ferroptosis, and disturbances in mitophagy, autophagy, and endo/lysosomal functions. This study investigated the cellular responses triggered by two structurally similar but functionally distinct Aβ42 preparations (NaOH-Aβ42 and NH4OH

Biography:

Alp Yigit Ozdemir, M.Sc., graduated with high honors and ranked 2nd in his class from Hacettepe University’s Department of Biology. He focused on amyloid beta toxicity and the neuroprotective effects of α-tocopherol and α-tocotrienol, publishing his findings (DOI: 10.55730/1300- 0152.2625). He is currently pursuing a Ph.D. in the Animal Physiology Department at Charles University under RNDr. Vladimir Rudajev. Ozdemir specializes in cell membrane properties and the effects of amyloid beta on SH-SY5Y cells. Additionally, he recently published a study examining how two distinct Amyloid β42 (Aβ42) preparations induce different cell death pathways (DOI: 10.1186/s11658-024-00657-8).

Research Interest:

Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β42 (Aβ42) protein, forming toxic aggregates that damage neuronal cells. Various cell death pathways are linked to its activity, including apoptosis, necroptosis, pyroptosis, oxidative stress, ferroptosis, and disturbances in mitophagy, autophagy, and endo/lysosomal functions. This study investigated the cellular responses triggered by two structurally similar but functionally distinct Aβ42 preparations (NaOH-Aβ42 and NH4OH-Aβ42) using differentiated SH-SY5Y neuroblastoma cells. Despite the similar appearance in both preparations in dynamic light scattering and atomic force microscopy analysis, they triggered different cellular responses. NaOH-Aβ42 mainly causes mitochondrial dysfunction and impaired energy metabolism by increasing the production of reactive oxygen, which can cause a decline in ATP production. However, NH4OH-Aβ42 induced early apoptosis and the formation of necrosomes, leading to necroptosis. Notably, NH4OH-Aβ42 also activated the heat shock protein (Hsp)27 expression, which helps mitigate cellular stress. Both Aβ preparations elevated levels of general stress markers like Hsp70 and Hsp90, indicating a broad stress response. Interestingly, the toxicity of NaOH-Aβ42 was linked to the presence of ganglioside GM1, while NH4OH-Aβ42's toxic effects occurred independently. These findings suggest that the specific structures of Aβ42 species are crucial for their toxic features. The presented differences between NaOH-Aβ42 and NH4OH-Aβ42 preparations show the importance of evaluating varieties of Aβ42 in AD research. In conclusion, these variations in Aβ42 oligomers significantly influence the toxicity and trigger very specific cellular stress responses, emphasizing the importance of aggregate specificity in understanding AD.