Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease  

作　　者：Gabriela Seplovich Yazan Bouchi Juan Pablo de Rivero Vaccari Jennifer C.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref Kevin K.Wang J.Adrian Tyndall Binu Tharakan Firas Kobeissy 

机构地区：[1]Department of Surgery,Morehouse School of Medicine,Atlanta,GA,USA [2]Department of Neurobiology,Center for Neurotrauma,Multiomics&Biomarkers(CNMB),Neuroscience Institute,Morehouse School of Medicine,Atlanta,GA,USA [3]Department of Neurological Surgery and the Miami Project to Cure Paralysis,University of Miami Miller School of Medicine,Miami,FL,USA [4]Division of Pediatric Critical Care,Department of Pediatrics,University of Miami Miller School of Medicine,Miami,FL,USA [5]Department of Pediatrics,Emory University,Atlanta,GA,USA [6]Department of Neurosurgery,Children’s Healthcare of Atlanta,Atlanta,GA,USA [7]Department of Chemistry and Biochemistry,Texas Tech University,Lubbock,TX,USA [8]Morehouse School of Medicine,Atlanta,GA,USA

出　　处：《Neural Regeneration Research》2025年第6期1644-1664,共21页中国神经再生研究（英文版）

摘　　要：Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关 键 词：Alzheimer's disease caspase-1 chronic traumatic encephalopathy INFLAMMASOMES NEURODEGENERATION neuroinflammation NLRP1 NLRP3 PYROPTOSIS TAUOPATHY traumatic brain injury 

分 类 号：R651.15[医药卫生—外科学] R749.16[医药卫生—临床医学]