Alzheimer’s Disease and Age-Related Macular Degeneration: Shared and Distinct Immune Mechanisms

Academic Background Alzheimer’s disease (AD) and age-related macular degeneration (AMD) are the leading causes of cognitive impairment and vision loss in the elderly population worldwide. Although they affect different organs (the brain and the retina, respectively), recent studies have revealed shared pathological features, such as β-amyloid (Aβ) ...

Microglia Transcriptional States and Their Functional Significance: Context Drives Diversity

Academic Background Microglia are the only resident macrophages in the central nervous system (CNS) and play critical roles in development, homeostasis, and disease. Traditionally, microglia were viewed as homogeneous “resting” or “activated” states, but the advent of single-cell sequencing technologies has revealed their remarkable transcriptional...

Inflammasome Signaling in Astrocytes Modulates Hippocampal Plasticity

Academic Background In recent years, the role of immune signaling pathways in nervous system homeostasis has garnered increasing attention. Traditionally, the inflammasome, a core complex of innate immunity, was thought to activate only during infection or tissue damage, participating in pathological processes through caspase-1-mediated pyroptosis ...

Complex Neural-Immune Interactions Shape Glioma Immunotherapy

1. Academic Background Glioblastoma (GBM) and pediatric diffuse midline gliomas (e.g., H3K27M-mutant) are among the most aggressive tumors of the central nervous system (CNS), with limited efficacy from conventional treatments (surgery, radiotherapy, chemotherapy). For decades, the CNS was considered to have “immune privilege,” meaning the immune s...

Interleukin-34-Dependent Perivascular Macrophages Promote Vascular Function in the Brain

Academic Background Macrophages in the central nervous system (CNS) include microglia and border-associated macrophages (BAMs). BAMs are distributed in the meninges, choroid plexus, and perivascular spaces, with perivascular macrophages (PVMs) being closely associated with cerebrovascular function. However, the mechanisms underlying BAM maintenance...

Direct Microglia Replacement Reveals Pathologic and Therapeutic Contributions of Brain Macrophages to a Monogenic Neurological Disease

Academic Background Krabbe disease (also known as globoid cell leukodystrophy, GLD) is a fatal pediatric neurodegenerative disorder caused by mutations in the galactosylceramidase (GALC) gene. A hallmark pathological feature of this disease is the presence of lipid-laden globoid cells (GCs) in the central nervous system (CNS). Currently, hematopoie...

Monocytes Can Efficiently Replace All Brain Macrophages and Fetal Liver Monocytes Can Generate Bona Fide Sall1+ Microglia

Academic Background The homeostasis of the central nervous system (CNS) relies on two key types of macrophages: microglia and border-associated macrophages (BAMs). Traditionally, microglia are believed to originate from the embryonic yolk sac and possess lifelong self-renewal capabilities, while bone marrow (BM)-derived monocytes in adults cannot r...

Unconventional Secretion of Park7 Requires Lysosomal Delivery via Chaperone-Mediated Autophagy and Specialized SNARE Complex

1. Research Background The Parkinson’s disease-associated protein PARK7/DJ-1 (hereafter referred to as PARK7) is a multifunctional protein that plays critical roles in various pathological conditions including neurodegenerative diseases, cancer, and inflammation. Despite lacking a conventional N-terminal signal peptide sequence, PARK7 can be secret...

The Interpeduncular Nucleus Blunts the Rewarding Effect of Nicotine

Nicotine is the primary addictive substance in tobacco, promoting smoking behavior by activating the brain’s dopamine reward system. Although the mechanisms of nicotine addiction have been extensively studied, the specific pathways through which it acts in the brain, particularly how it modulates reward and aversion through different neural circuit...

Alpha-Synuclein Mutations Mislocalize Cytoplasmic p300 Compromising Autophagy, Which Is Rescued by ACLY Inhibition

Academic Background Parkinson’s Disease (PD) is the second most common neurodegenerative disorder, characterized by motor dysfunction, loss of dopaminergic neurons, and abnormal accumulation of alpha-synuclein (α-syn). Although the cause of most PD cases remains unclear, approximately 5%-10% of cases are due to monogenic mutations. The SNCA gene, w...