Biol. Chem. 2018; 399(1): 55–61 Minireview Nguyen Thi Thanh Ho, Arne Kutzner and Klaus Heese* Brain plasticity, cognitive functions and neural stem cells: a pivotal role for the brain-specific neural master gene |-SRGAP2–FAM72-|  https://doi.org/10.1515/hsz-2017-0190 Received July 7, 2017; accepted August 11, 2017 Abstract: Due to an aging society with an increased demen- tia-induced threat to higher cognitive functions, it has become imperative to understand the molecular and cellu- lar events controlling the memory and learning processes in the brain. Here, we suggest that the novel master gene pair |-SRGAP2–FAM72-|  (SLIT-ROBO Rho GTPase activating the protein 2, family with sequence similarity to 72) reveals a new dogma for the regulation of neural stem cell (NSC) gene expression and is a distinctive player in the control of human brain plasticity. Insight into the specific regulation of the brain-specific neural master gene |-SRGAP2–FAM72-|  may essentially contribute to novel therapeutic approaches to restore or improve higher cognitive functions. Keywords: brain; FAM72; learning; memory; neuron; p17; SRGAP2; synapse. Introduction Dementia, caused by brain cell damage induced by various factors such as Alzheimer’s disease, cerebro-/car- diovascular diseases, stroke or other injuries, is a major concern in an aging society, and increasing efforts are underway to develop new cures for aging-related neuro- degenerative diseases (Kumari and Heese, 2010; Heese, 2015; Nagata et al., 2016; Pini et al., 2016; Vijayan and Reddy, 2016; Wyss-Coray 2016; Tarantini et al., 2017; Yang et al., 2017). The World Health Organization (WHO) has taken a leadership role in establishing a global demen- tia action plan to translate and set research priorities to reduce the global burden of dementia (Shah et al., 2016). Although the use of stem cell-based therapies is highly promising, the transplantation of autologous stem cells and the control of specific neural differentiation remain major challenges to the development of these thera- pies (Pramanik et al., 2017). The recent discovery of the master gene |-SRGAP2–FAM72-|  has provided new insight into brain plasticity (Subramanian and Nedivi, 2016; Ho et al., 2017). After a brief recapitulation of fundamental background information [neural stem cells (NSCs), syn- aptic plasticity, memory and learning], we present a new hypothesis for the regulation of NSC gene expression and discuss the novel master gene |-SRGAP2–FAM72-|  as a key regulator of mechanisms involved in these memory and learning processes, which require tight control of NSC pro- liferation and differentiation. Background Memory and learning The hippocampus is essential for learning new information and for consolidating this new information to long-term memory, which is associated with newly established stable and permanent changes in the neural network (synaptic plasticity) spread across the entire brain (Squire, 2009). Historically, memory and learning processes were consid- ered to have two distinctive components, namely, short- and long-term memory, with new gene expression character- izing the latter (Squire et al., 1993; Squire, 2009). Further studies revealed that these multiphasic processes consist of at least three phases, with an additional intermediate phase (Ghirardi et al., 1995; Saitoh and Inokuchi, 2000; Grimes et al., 2012). At the molecular level, key players involved in these mechanisms include, among others, the *Corresponding author: Klaus Heese, Graduate School of Biomedical Science and Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 133-791, Republic of Korea, e-mail: klaus@hanyang.ac.kr. http://orcid.org/0000-0002-0027-6993 Nguyen Thi Thanh Ho: Graduate School of Biomedical Science and Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong- gu, Seoul 133-791, Republic of Korea Arne Kutzner: Department of Information Systems, College of Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong- gu, Seoul 133-791, Republic of Korea Bereitgestellt von | De Gruyter / TCS Angemeldet Heruntergeladen am | 14.12.17 14:05