Investigation of Alzheimer's Disease‐Associated effect of SPOCK1 Protein on Apoptosis in Nerve Cells

Alzheimer's Association International Conference, Toronto, Kanada, 27 - 31 Temmuz 2025, cilt.21, sa.105818, ss.23, (Özet Bildiri)

Investigation of Alzheimer's Disease-Associated effect of SPOCK1 Protein on Apoptosis in Nerve Cells

Emilia QOMI EKENEL¹, Pardis SAFERNEZHAD², Deniz Cansen Kahraman¹, Çağdaş Devrim SON², Yeşim AYDIN SON¹

¹Graduate School of Informatics, Middle East Technical University, Ankara, Turkey

²Department of Biological Sciences, Middle East Technical University, Ankara, Turkey

Background: SPOCK1, a member of the SPARC family, is highly expressed in breast,

lung, prostate, and liver cancer. Various studies have demonstrated that SPARC family

proteins play a crucial role in the development and diseases of the central nervous

system (CNS). However, the role of SPOCK1, a member of the SPARC family, in CNS

diseases—particularly Alzheimer’s disease—remains unknown. Previously, we have

reported an association between SPOCK1 variants and LOAD in a genome-wide

association studies (GWAS) meta-analysis. Based on our observation and the recent

literature on SPOCK1, we explored the role of SPOCK1 in different neuronal cells to

understand its possible function in Alzheimer’s pathogenesis.

Methods: Human astroglia (SVGp12), microglial (HMC3), and neuroblastoma

(SH-SY5Y) cell lines expressing fluorescently tagged SPOCK1 and un-tagged

SPOCK1 were used to investigate the expression and localization of SPOCK1 via

immunocytochemistry (ICC) and confocal image analysis. It is well known that

Alzheimer’s disease is associated with death mechanisms in nerve cells. To investigate

the molecular basis of Alzheimer’s disease based on the possible unpredicted

interactions and roles of SPOCK1 protein in mitochondrial cell death, SPOCK1 gene

silencing and over-expression effects on apoptosis were detected via TUNEL assay

in human astroglia (SVGp12), microglial (HMC3), and neuroblastoma (SH-SY5Y) cell

lines.

Results: Our results based on immunocytochemistry (ICC) and confocal image analysis

with various organelle markers showed for the first time that SPOCK1 is localized at

the mitochondria of all the microglial, neuroblastoma, and astroglia cells. Moreover,

apoptosis was detected in SPOCK1 over-expressed astrocyte cells. However in

SPOCK1 over-expressing neuroblastoma cells, proliferaiton is observed, and when

SPOCK1 was silenced, apoptotic cells were decreased. In microglial cells, no significant

change was observed when SPOCK1 was over-expressed or silenced.