z-bio 2025-07-03 3027

　　In recent years, the field of neuroimmunity has developed rapidly, and 15 disease modification drugs have emerged. These drugs can effectively prevent new lesions in patients' optic nerve, brain and spinal cord, reduce disease recurrence, and make patients' life and work close to normal.

　　In recent years, research has found that neuroimmunity and inflammation are common pathophysiological mechanisms of all central nervous system diseases. Coupled with the successful experience in the treatment of neuroimmune diseases, the exploration of immune regulation and treatment in diseases such as stroke, Alzheimer's disease, Parkinson's disease, and other diseases has brought new hope to the treatment of these diseases.

　　To this end, Science specially invited the authoritative expert in the field of neuroimmunity, Professor Shi Fudong from Beijing Tiantan Hospital Affiliated to Capital Medical University/Tianjin Medical University General Hospital and Professor Wee Yong from Calgary University in Canada to jointly write a review article entitled "Neuroinflammation across neurological diseases".

　　In this article, the mechanism of action of neuroinflammation in different neurological diseases is deeply analyzed, and the direction is pointed out for the research and development of new therapies.

　　It is worth mentioning that this is the first science official issue of Beijing Tiantan Hospital affiliated to Capital Medical University as the first unit.

　　What is neuroinflammation? Why is this critical?

　　Neuroinflammation, simply put, is an immune response to injury by the central nervous system (CNS), mainly manifested in the activation of microglia and astrocytes, as well as the infiltration of peripheral immune cells (such as lymphocytes and neutrophils).

　　Under normal circumstances, it is the "protective mechanism" of the body trying to repair damage and remove harmful substances; but when this response is dysregulated, over-activated or persists, it will in turn aggravate nerve damage and form a vicious cycle of "neuroinflammatory-neurodegenerative transformation".

　　Research points out that from acute stroke to chronic Alzheimer's disease, neuroinflammation occurs in almost all neurological diseases. It is not only an "accelerator" for disease progression, but also one of the core causes of patients' disability and cognitive decline.

　　According to statistics, neurological diseases have become the most common disease category in the world, and targeted neuroinflammation is an important breakthrough to reduce this global burden.

　　In different diseases, neuroinflammation has its own "personality"

　　Although neuroinflammation is a common feature, its "performance" and "rhythm" are very different in different diseases.

　　In multiple sclerosis (MS), neuroinflammation is more like a "early-onset immune storm": peripheral immune cells (especially T cells and B cells) infiltrate the central nervous system in large quantities in the early stage, and microglia show destructiveness from the beginning, constantly attacking the nerve myelin sheath, leading to the formation of lesions and recurrence of repeated lesions.

　　Stroke is a "chain reaction after acute injury": after blood vessels are blocked or ruptured, the "risk signals" released by the rapid death of nerve cells (such as DAMPs) will quickly activate microglia, and within a few hours, neutrophils, macrophages, etc. will pour into the brain tissue, which may help clear necrotic tissue in the early stage, but persistent inflammation will aggravate secondary brain damage and even trigger long-term cognitive decline.

　　In Alzheimer's disease (AD) and Parkinson's disease (PD), neuroinflammation is more like a "chronic protracted war": first, misfolded proteins (such as β-amyloid and α-synuclein) continue to gather, and microglia will actively remove these "garbage" in the early stage to play a protective role; but after being stimulated for a long time, microglia will "out of control", releasing toxins and pro-inflammatory factors, which will accelerate nerve cell death.

　　"Deadly interaction" between cells: How does inflammation become more and more intense?

　　Research has found that the aggravation of neuroinflammation cannot be separated from the "mutual cooperation" between cells. After T cells enter the central nervous system, they will "collude" with microglia to amplify the inflammatory response; astrocytes will change to a "neurotoxic phenotype" under the stimulation of signals released by microglia (such as inflammatory factors), further destroying neural tissue.

　　More importantly, as the disease progresses, neuroinflammation will gradually be "localized" within the central nervous system - especially the continuous activation of microglia. This means that to block inflammation, the drug must be able to penetrate the blood-brain barrier and act directly on immune cells in the center.

　　The dawn of new therapies: from targeting the periphery to penetrating the center

　　At present, some progress has been made in the treatment of neuroinflammation. In multiple sclerosis, drugs that target peripheral immune cells (such as natalizumab that prevents immune cells from entering the center) can effectively reduce recurrence; but for advanced diseases and other neurological diseases, drugs that penetrate the blood-brain barrier are needed.

　　Potential therapies include:

　　BTK inhibitors: This type of drug can inhibit the excessive activation of microglia and has shown an effect on reducing disability progression in clinical trials of progressive multiple sclerosis;

　　CAR-T cell therapy: precisely targets inflammation-related cells by modifying immune cells;

　　New use of old medicines: For example, hydroxychloroquine can regulate microglia activity, and niacin can enhance its ability to remove toxins;

　　TREM2 agonist: Enhance microglia's ability to remove misfolded proteins and shows potential in Alzheimer's disease model.

　　The study also emphasized that single therapy is difficult to work and a "joint strategy" may be needed in the future - to inhibit neuroinflammation and to target the cause (such as clearing misfolded proteins).

　　未来挑战：平衡“保护”与“破坏”

　　尽管前景可期，神经炎症的治疗仍面临挑战。例如，小胶质细胞在疾病早期可能发挥保护作用（如清除毒素），晚期才转为破坏，因此治疗时机的选择至关重要；此外，如何精准靶向炎症的“有害面”，同时保留其“有益面”，仍是科学家需要攻克的难题。

　　但可以确定的是，随着对神经炎症机制的深入理解，我们离“驯服”这一多种神经系统疾病的“共同推手”越来越近。这不仅能为患者带来新的治疗选择，更有望大幅减轻全球神经系统疾病的负担。