The amyloid cascade hypothesis has predominately been used to describe the pathogenesis of Alzheimer’s disease (AD) for decades, as Aβ oligomers are thought to be the prime cause of AD. Meanwhile, the neurotrophic factor hypothesis has also been proposed for decades. Accumulating evidence states that the amyloidogenic process and neurotrophic dysfunction are mutually influenced and may coincidently cause the onset and progress of AD. Meanwhile, there are intracellular regulators participating both in the amyloidogenic process and neurotrophic pathways, which might be the common original causes of amyloidogenesis and neurotrophic dysfunction. In this review, the current understanding regarding the role of neurotrophic dysfunction and the amyloidogenic process in AD pathology is briefly summarized. The mutual influence of these two pathogenesis pathways and their potential common causal pathway are further discussed. Therapeutic strategies targeting the common pathways to simultaneously prevent amyloidogenesis and neurotrophic dysfunction might be anticipated for the disease-modifying treatment of AD.

Orexins are a family of neuropeptides secreted by neurons in the lateral hypothalamus (LH). These peptides act widespreadly across the body by interacting with specific orexin receptors on target cells, which comprise the orexinergic system. Emerging evidence has revealed that the orexinergic system is tightly associated with neuropsychiatric disorders; however, the underlying mechanisms require further exploration. Neuropsychiatric disorders have also been associated with neuroplasticity, while orexins have been shown to play regulatory roles in neuronal plasticity. As such, this review aims to summarize the recent progress of research investigating the roles of the orexinergic system in neuronal plasticity and associated neuropsychiatric disorders, including addiction, depression, and schizophrenia, which may provide novel insights into the mechanism of the orexinergic system in the pathogenesis of these neuropsychiatric disorders.

Conventional dendritic cells (cDCs) are pivotal antigen-presenting cells (APCs) with critical roles in immune regulation, yet their subset classification remains ambiguous due to phenotypic overlap with macrophages and monocytes, particularly in the spleen. This study employed multi-parametric flow cytometry and clodronate liposome (CL) depletion to systematically re-evaluate splenic CD11c ^high MHCII ^high cDCs in C57BL/6 mice. We identified three novel subsets: (1) a tissue-resident T-cell zone macrophage (TZM)-like population (F4/80 ^inter-low CX3CR1 ⁺ MERTK ⁺ ) constituting 0.59% of cDC2s with >10-fold CL-depletion resistance ( p < 0.0001); (2) a resident F4/80 ^high APC subset (CCR2 ⁻ Ly6C⁻) accounting for 2.7% of cDC2s with CL-sensitivity; (3) unconventional CD4⁺CD8α⁺ hybrids present in 2.57% of cDC2 and some cDC1s. These findings demonstrate unprecedented cDC plasticity driven by microenvironmental signals, revising conventional classification frameworks and proposing new targets for DC-based immunotherapies in autoimmunity and cancer. Our phenotypic mapping provides a foundational framework for future functional investigations into these novel subsets.

Neuroinflammation is increasingly recognized as a key contributor and amplifier associated with the pathogenesis of Alzheimer’s disease (AD) and Parkinson’s disease (PD). Neuroinflammation occurs throughout various stages of these diseases with expanding complexity. Currently, no effective therapies exist that specifically target neuroinflammatory processes in these disorders. In this review, we synthesize current understanding of central and peripheral inflammatory mechanisms implicated in both diseases. We illustrate how endogenous pathological triggers, such as amyloid-β (Aβ) peptide, hyperphosphorylated tau, and α-synuclein, activate glial cells, contributing to chronic neuroinflammation that exacerbates neurodegeneration. Additionally, peripheral factors, including systemic inflammation, environmental exposures, and gut-brain axis interactions, are discussed for their roles in modulating neuroinflammatory responses. Notably, the underappreciated roles of oligodendrocyte precursor cells and oligodendrocytes in neuroimmune crosstalk are also highlighted. Advanced methodologies, including glial cell imaging, single-cell transcriptomics, and human induced pluripotent stem cell-derived organoid models, are providing unprecedented insights into the molecular and cellular mechanisms underlying neuroinflammation. Finally, we evaluate emerging therapeutic strategies and ongoing clinical trials targeting neuroinflammatory pathways and analyze the potential of immunomodulatory approaches to slow disease progression. This comprehensive review emphasizes that precise targeting of neuroinflammation represents a tractable strategy for developing effective disease‑modifying treatments for AD and PD.

Background: Parkinson's disease (PD), the second most prevalent age‐associated neurodegenerative disorder, is characterized by the degeneration and loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SN). Among the intricate pathophysiological processes of PD, chronic neuroinflammation has emerged as a pivotal hallmark in the pathogenesis of PD. The aminoacyl tRNA synthetase complex has been reported to play an important role in modulating the immune response and associated diseases. Nevertheless, the specific functions and implications of the complex in PD remain largely unclear.Methods: Enzyme‐linked immunosorbent assay (ELISA) was used to investigate levels of AIMP1 and TNF‐α. An in vivo PD model was constructed by administering 1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) in mice. A PD cell model was established by treating SH‐SY5Y cells with 1‐methyl‐4‐phenylpyridinium (MPP⁺). Pole test was performed to assess the motor function of mice. DA neuron survival and microglia activation were detected by immunofluorescence. Western blot and qPCR were used to detect the levels of tyrosine hydroxylase (TH) and inflammatory cytokines. RNA‐Seq analysis was performed to explore possible mechanisms.Results: The levels of AIMP1, a co‐factor of the aminoacyl tRNA synthetase complex, were significantly elevated in the blood of PD patients. Aimp1 knockout or knockdown remarkably improved the viability of DA neurons in the MPTP‐induced mouse model of PD. Aimp1 deficiency reduced microglial activation in PD mice. RNA‐Seq analysis revealed that AIMP1 promoted microglial inflammatory response. Moreover, the AIMP1‐induced microglial activation was CD23 dependent.Conclusions: Collectively, our findings indicate that AIMP1 derived from DA neurons exacerbates neuroinflammation, promotes the death of DA neurons and contributes to the development of PD. This study offers novel insights into the molecular mechanisms underlying PD and blocking the AIMP1‐CD23 signaling pathway potentially serves as a therapeutic strategy for PD.