医学最新文献

Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory damage. The expression of the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis exhibits significant differences before and after injury. Recent studies have revealed that the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis is closely associated with secondary inflammatory responses and the recruitment of immune cells following spinal cord injury, suggesting that this axis is a novel target and regulatory control point for treatment. This review comprehensively examines the therapeutic strategies targeting the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis, along with the regenerative and repair mechanisms linking the axis to spinal cord injury. Additionally, we summarize the upstream and downstream inflammatory signaling pathways associated with spinal cord injury and the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis. This review primarily elaborates on therapeutic strategies that target the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the latest progress of research on antagonistic drugs, along with the approaches used to exploit new therapeutic targets within the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the development of targeted drugs. Nevertheless, there are presently no clinical studies relating to spinal cord injury that are focusing on the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis. This review aims to provide new ideas and therapeutic strategies for the future treatment of spinal cord injury.

The complex morphological, anatomical, physiological, and chemical mechanisms within the aging brain have been the hot topic of research for centuries. The aging process alters the brain structure that affects functions and cognitions, but the worsening of such processes contributes to the pathogenesis of neurodegenerative disorders, such as Alzheimer's disease. Beyond these observable, mild morphological shifts, significant functional modifications in neurotransmission and neuronal activity critically influence the aging brain. Understanding these changes is important for maintaining cognitive health, especially given the increasing prevalence of age-related conditions that affect cognition. This review aims to explore the age-induced changes in brain plasticity and molecular processes, differentiating normal aging from the pathogenesis of Alzheimer's disease, thereby providing insights into predicting the risk of dementia, particularly Alzheimer's disease.

JOURNAL/nrgr/04.03/01300535-202508000-00002/figure1/v/2024-09-30T120553Z/r/image-tiff Traumatic brain injury is a prevalent disorder of the central nervous system. In addition to primary brain parenchymal damage, the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury; however, the underlying pathogenesis remains unclear, and effective intervention methods are lacking. Intestinal dysfunction is a significant consequence of traumatic brain injury. Being the most densely innervated peripheral tissue in the body, the gut possesses multiple pathways for the establishment of a bidirectional "brain-gut axis" with the central nervous system. The gut harbors a vast microbial community, and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal, hormonal, and immune pathways. A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated complications. We comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury, with a specific focus on the complex biological processes of peripheral nerves, immunity, and microbes triggered by traumatic brain injury, encompassing autonomic dysfunction, neuroendocrine disturbances, peripheral immunosuppression, increased intestinal barrier permeability, compromised responses of sensory nerves to microorganisms, and potential effector nuclei in the central nervous system influenced by gut microbiota. Additionally, we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain injury. This review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effects of the "brain-gut-microbiota axis."

JOURNAL/nrgr/04.03/01300535-202508000-00025/figure1/v/2024-09-30T120553Z/r/image-tiff TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon. TAU is missorted and aggregated in an array of diseases known as tauopathies. Microtubules are essential for neuronal function and regulated via a complex set of post-translational modifications, changes of which affect microtubule stability and dynamics, microtubule interaction with other proteins and cellular structures, and mediate recruitment of microtubule-severing enzymes. As impairment of microtubule dynamics causes neuronal dysfunction, we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule dynamics. We therefore aimed to study the effects of a disease-causing mutation of TAU (P301L) on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics, to assess whether P301L-TAU causes stability-changing modifications to microtubules. To investigate TAU localization, phosphorylation, and effects on tubulin post-translational modifications, we expressed wild-type or P301L-TAU in human MAPT -KO induced pluripotent stem cell-derived neurons (iNeurons) and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU (pR5 mice). Human neurons expressing the longest TAU isoform (2N4R) with the P301L mutation showed increased TAU phosphorylation at the AT8, but not the p-Ser-262 epitope, and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons. P301L-TAU showed pronounced somatodendritic presence, but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU. P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation, but reduced acetylation, of microtubules compared with non-transgenic littermates. In sum, P301L-TAU results in changes in microtubule PTMs, suggestive of impairment of microtubule stability. This is accompanied by missorting and aggregation of TAU in mice but not in iNeurons. Microtubule PTMs/impairment may be of key importance in tauopathies.