Page 50 - Q. Neuroscience

[Q. Neuroscience-30]

SPON1 Reduces Amyloid Beta and Ameliorates Cognitive

Impairment and Memory Dysfunction in Alzheimer’s Disease

Mouse Model

Soo Yong Park¹, Joo Yeong Kang¹, Taehee Lee¹, Donggyu Nam¹, Chang-Jin Jeon², Jeong Beom Kim¹

¹School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, South Korea,

²DDepartment of Biology, Kyungpook National University, Dague 41566, South Korea

Alzheimer’s disease (AD) is a complex age-related neurodegenerative disease that is the most common form of
dementia. However, the cure for AD has not yet been developed. The accumulation of amyloid-beta (Aβ) is

considered one of the hallmarks of AD. Beta-secretase BACE1 is the initiating enzyme in the amyloidogenic pathway.
Inhibiting BACE1 could reduce the amount of Aβ, but this would also prohibit the other functions of BACE1 in brain

physiological activity. SPON1 binds to BACE1 binding site of amyloid precursor protein (APP) and block the initiating
amyloidogenesis. Here, we demonstrated the effect of SPON1 in Aβ reduction in vitro neural cells and in vivo AD

mouse model. We engineered induced neural stem cells (iNSCs) to express Spon1. iNSCs harboring mouse Spon1
secreted Spon1 protein and reduced the quantity of Aβ when co-cultured with Aβ-secreting Neuro 2a cells. Human

SPON1 gene itself also reduced Aβ in HEK 293T cells expressing human APP transgene with AD-linked mutations
through gene delivery. We also showed that injecting SPON1 reduced the amount of Aβ and ameliorate cognitive

dysfunction and memory impairment in AD mice.