title: Thinking outside the brain for cognitive improvement: Is peripheral immunomodulation on the way?
abstract: Cognitive impairment is a devastating condition commonly observed with normal aging and neurodegenerative disorders such as Alzheimer's Disease (AD). Although major efforts to prevent or slow down cognitive decline are largely focused within the central nervous system (CNS), it has become clear that signals from the systemic milieu are closely associated with the dysfunctional brain. In particular, the bidirectional crosstalk between the CNS and peripheral immune system plays a decisive role in shaping neuronal survival and function via neuroimmune, neuroendocrinal and bioenergetic mechanisms. Importantly, it is emerging that some neuroprotective and cognition-strengthening drugs may work by targeting the brain-periphery interactions, which could be intriguingly achieved without entering the CNS. We describe here how recent advances in dissecting cognitive deficits from a systems-perspective have contributed to a non-neurocentric understanding of its pathogenesis and treatment strategy. We also discuss the therapeutic and diagnostic implications of these exciting progresses and consider some key issues in the clinical translation. This article is part of a Special Issue entitled 'Neuroimmunology and Synaptic Function'.
authors: Nanjing University of Chinese Medicine Affiliated Hospital, Nanjing 210029, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: xiaozhengcpu@gmail.com.
authors: Xiao
authors: X
authors: Zheng
authors: Zhong Da Hospital, Southeast University, Nanjing 210009, China.
authors: Xueli
authors: X
authors: Zhang
authors: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors: An
authors: A
authors: Kang
authors: MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital/Harvard Medical School, Boston 02129, United States.
authors: Chongzhao
authors: C
authors: Ran
authors: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors: Guangji
authors: G
authors: Wang
authors: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: hhp_770505@hotmail.com.
authors: Haiping
authors: H
authors: Hao
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology / Q000382:microbiology; D000818:Animals; D001921:Brain / Q000276:immunology* / Q000382:microbiology; D001927:Brain Diseases / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D001930:Brain Injuries / Q000276:immunology / Q000382:microbiology; D003071:Cognition / Q000502:physiology*; D000069196:Gastrointestinal Microbiome / Q000276:immunology / Q000502:physiology; D006801:Humans; D006816:Huntington Disease / Q000276:immunology / Q000382:microbiology; D007107:Immune System / Q000382:microbiology / Q000502:physiology*; D056747:Immunomodulation; D020521:Stroke / Q000276:immunology / Q000382:microbiology
keywords: Brain–gut axis; CNS drug discovery; Cognitive decline; Gut microbiota; Neuroimmune interaction; Peripheral targets