Pad2 deletion induces anxiety‑like behaviors and memory deficits in mice

Citrullination, the deimination of peptidylarginine residues into peptidylcitrulline catalyzed by the peptidylarginine deiminase (PADs), has been confirmed as a unique form of posttranslational modification of proteins. Among the five isoforms of PADs, PAD2 is a main PAD enzyme expressed in central nervous system (CNS). Previous studies reported that citrullinated proteins catalyzed by PAD2 was increasingly associated with neurological disorders such as Alzheimer's disease, prion disease and Multiple Sclerosis. However, the physiological role of PAD2 in the CNS are still poorly elucidated. Here we reported that Pad2 knockout (KO) mice exhibited significantly increased anxiety level and impaired memory capacity. Furthermore, Western Blot analysis, immunohistochemistry and proteomics revealed alterations in synaptic-related proteins and dendritic spines in hippocampus of Pad2 KO animals. These findings indicated that Pad2 plays an important function in the CNS, which is implicated in the regulation of emotion and cognitive capacity.

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Journal
Brain Research Bulletin
Published
2025-04-04
DOI
https://doi.org/10.1016/j.brainresbull.2025.111327
Primary Topic
Genetics and Neurodevelopmental Disorders
Type
article
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article

Pad2 deletion induces anxiety‑like behaviors and memory deficits in mice

Changhong Shi, Xiaoqiang Lv, Cunzhi Li, Zhiyong Liu et al.
Brain Research Bulletin
Genetics and Neurodevelopmental Disorders
article

Pad2 deletion induces anxiety‑like behaviors and memory deficits in mice

Changhong Shi, Xiaoqiang Lv, Cunzhi Li, Zhiyong Liu, Yongchao Gao, Hui Deng, Yuhao Zhang, Bin Zhao, Wenzhi Gao, Junhong Gao
article en

Abstract

Citrullination, the deimination of peptidylarginine residues into peptidylcitrulline catalyzed by the peptidylarginine deiminase (PADs), has been confirmed as a unique form of posttranslational modification of proteins. Among the five isoforms of PADs, PAD2 is a main PAD enzyme expressed in central nervous system (CNS). Previous studies reported that citrullinated proteins catalyzed by PAD2 was increasingly associated with neurological disorders such as Alzheimer's disease, prion disease and Multiple Sclerosis. However, the physiological role of PAD2 in the CNS are still poorly elucidated. Here we reported that Pad2 knockout (KO) mice exhibited significantly increased anxiety level and impaired memory capacity. Furthermore, Western Blot analysis, immunohistochemistry and proteomics revealed alterations in synaptic-related proteins and dendritic spines in hippocampus of Pad2 KO animals. These findings indicated that Pad2 plays an important function in the CNS, which is implicated in the regulation of emotion and cognitive capacity.

Brain Research BulletinVol. 224
Northwestern Polytechnical University (CN), Northwest University (CN), Microbiology Institute of Shaanxi (CN), Air Force Medical University (CN)
Openalex Percentile: Top 92%
Genetics and Neurodevelopmental Disorders
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Pad2 deletion induces anxiety‑like behaviors and memory deficits in mice — Changhong Shi, Xiaoqiang Lv, et al. · Brain Research Bulletin (2025) | TGRS Research Map | TGRS