Page 49 - Q. Neuroscience

SPON1 inhibits Amyloidogenesis and improves cognitive and
memory functionality in Alzheimer’s disease mouse model.
Soo Yong Park, Joo Yeong Kang, Taehee Lee, Donggyu Nam, & Jeong Beom Kim
Stem Cell Research Center, School of Life Sciences, Ulsan National Institute of Science
and Technology (UNIST), Ulsan, South Korea
BACKGROUND AIM
Alzheimer’s disease (AD) is a complex age-related Here, we show the effect of SPON1 in Aβ reduction in
neurodegenerative disease and the most common form of vitro neural cells and in vivo AD mouse model. We
dementia. However, the cure for AD has not yet been focus on preventing Aβ synthesis in early stage of AD
developed. The accumulation of amyloid beta (Aβ) is pathology by blocking BACE1 cleavage site which is
considered as a one of the hallmarks of AD. the initiating enzyme in amyloidogenesis.
METHODS

We engineered induced neural stem cells (iNSCs) to express Spon1 and then co-cultured iNSCs with Aβ-secreting
Neuro 2A cells. The reduced amount of Aβ was confirmed by Aβ 42 and 40 ELISA. We also considered the SPON1
for development of AD gene therapy. Thus, human SPON1 was constructed in lentiviral vector and analyzed in
293T-APP cells by direct infection. Furthermore, The effect of SPON1 was evaluated in 5xFAD mouse model of AD.
Human SPON1-encoded lentiviral vectors were administrated into hippocampus and entorhinal cortex in early stage
of AD pathology. We performed Morris water maze test to analyze the cognitive and memory dysfunction and
observed the Aβ by immunohistochemical analysis and western blot.
RESULTS

Figure 1. We generated Spon1-secreting iNSCs and
confirmed Aβ reduction in co-culture with Neuro 2A cells
which secretes Aβ.

Figure 3. SPON1-injected 5xFAD mice ameliorates cognitive
Figure 2. We infected human SPON1 encoded in lentiviral impairment and memory dysfunction, which was proven by
vector into 293T-APP and found Aβ reduction without Morris water maze behavior test. Aβ oligomers and deposition
affecting endogenous gene expression related to Amyloid was reduced in SPON1-injected area.
pathway.
CONCLUSION REFERENCES ACKNOWLEDGEMENTS

In this study, we demonstrated Park, S.Y.; Kang, J.Y.; This work was supported by Bio &
the effects of SPON1 as a Lee, T.; Nam, D.; Jeon, Medical Technology Development
treatment option for AD. C.J.; Kim, J.B. SPON1 Program of the National Research
Can Reduce Amyloid
SPON1 administration Beta and Reverse Foundation funded by the Ministry of
reduced Aβ levels both in vitro Cognitive Impairment Science & ICT (Grant No.
and in vivo. In particular, the and Memory 2017M3A9C6033875).
direct injection of SPON1 into Dysfunction in Contact information
the animal model of AD Alzheimer’s Disease
improved the memory function Mouse Model. Cells Correspondence: Jeong Beom Kim
of mice. 2020, 9 jbkim@unist.ac.kr