The Latest Articles on Immunity and Aging and Neurodegenerative Diseases
Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.
This week, we would like to share several latest articles on Immunity and Aging and Neurodegenerative Diseases.
Title: Alzheimer's disease: From immunotherapy to immunoprevention
Authors: Mathias Jucker, Lary C. Walker
Type: Review
Abstract:
Recent Aβ-immunotherapy trials have yielded the first clear evidence that removing aggregated Aβ from the brains of symptomatic patients can slow the progression of Alzheimer's disease. The clinical benefit achieved in these trials has been modest, however, highlighting the need for both a deeper understanding of disease mechanisms and the importance of intervening early in the pathogenic cascade. An immunoprevention strategy for Alzheimer's disease is required that will integrate the findings from clinical trials with mechanistic insights from preclinical disease models to select promising antibodies, optimize the timing of intervention, identify early biomarkers, and mitigate potential side effects.
Access this article: https://doi.org/10.1016/j.cell.2023.08.021
Title: Proteostasis in T cell aging
Authors: A. Elisabeth Gressler, Houfu Leng, Heidi Zinecker, Anna Katharina Simon
Type: Review
Abstract:
Aging leads to a decline in immune cell function, which leaves the organism vulnerable to infections and age-related multimorbidities. One major player of the adaptive immune response are T cells, and recent studies argue for a major role of disturbed proteostasis contributing to reduced function of these cells upon aging. Proteostasis refers to the state of a healthy, balanced proteome in the cell and is influenced by synthesis (translation), maintenance and quality control of proteins, as well as degradation of damaged or unwanted proteins by the proteasome, autophagy, lysosome and cytoplasmic enzymes. This review focuses on molecular processes impacting on proteostasis in T cells, and specifically functional or quantitative changes of each of these upon aging. Importantly, we describe the biological consequences of compromised proteostasis in T cells, which range from impaired T cell activation and function to enhancement of inflamm-aging by aged T cells. Finally, approaches to improve proteostasis and thus rejuvenate aged T cells through pharmacological or physical interventions are discussed.
Access this article: https://doi.org/10.1016/j.smim.2023.101838
Title: Alzheimer’s disease: The role of T lymphocytes in neuroinflammation and neurodegeneration
Authors: Moses O. Asamu, Oladapo O. Oladipo, Oluseun A. Abayomi, Afeez A. Adebayo
Type: Research Article
Abstract:
Alzheimer’s disease, the leading cause of progressive cognitive decline globally, has been reported to be enhanced by neuroinflammation. Brain-resident innate immune cells and adaptive immune cells work together to produce neuroinflammation. Studies over the past decade have established the neuroimmune axis present in Alzheimer’s disease; the crosstalk between adaptive and innate immune cells within and outside the brain is crucial to the onset and progression of Alzheimer’s disease. Although the role of the adaptive immune system in Alzheimer's disease is not fully understood, it has been hypothesized that the brain's immune homeostasis is significantly disrupted, which greatly contributes to neuroinflammation. Brain-infiltrating T cells possess proinflammatory phenotypes and activities that directly contribute to neuroinflammation. The pro-inflammatory activities of the adaptive immune system in Alzheimer’s disease are characterized by the upregulation of effector T cell activities and the downregulation of regulatory T cell activities in the brain, blood, and cerebrospinal fluid. In this review, we discuss the major impact of T lymphocytes on the pathogenesis and progression of Alzheimer’s disease. Understanding the role and mechanism of action of T cells in Alzheimer’s disease would significantly contribute to the identification of novel biomarkers for diagnosing and monitoring the progression of the disease. This knowledge could also be crucial to the development of immunotherapies for Alzheimer’s disease.
Access this article: https://doi.org/10.1016/j.brainres.2023.148589
Title: A potential therapeutic target: The role of neutrophils in the central nervous system
Authors: Isabel Salken, Jose Javier Provencio, Aminata P. Coulibaly
Type: Review
Abstract:
Neutrophils play a critical role in immune defense as the first recruited and most abundant leukocytes in the innate immune system. As such, regulation of neutrophil effector functions have strong implications on immunity. These cells display a wide heterogeneity of function, including both inflammatory and immunomodulatory roles. Neutrophils commonly infiltrate the central nervous system (CNS) in response to varied pathological conditions. There is still little understanding of the role these cells play in the CNS in such conditions. In the present review, we will summarize what is known of neutrophil's role in cancer and Alzheimer's disease (AD), with a focus on highlighting the gaps in our understanding.
Access this article: https://doi.org/10.1016/j.bbih.2023.100688
Title: Development of neuropsychiatry over the last 30 years and the new era of Immuno-Psychiatry
Authors: Karl Bechtera
Type: Review
Abstract:
This is a narrative review about Neuropsychiatry, the development of Psychoneuroimmunology, and the progression to Immuno-Psychiatry (IP) over the last 30 years based on textbooks, journal articles and personal contributions.
Definitions, coverage and highlights in the development of neuropsychiatry document a change from focused individual organic diagnostic case reports to broader approaches (e.g., brain-mind relationships), or more specialized (e.g., neuroimaging perspective, neurogenetics, neuroplasticity) thereby achieving increasing clinical relevance, and advancing to recent highlights those being the developments in neurogenetics and psychoneuroimmunology. The latter has culminated in the emerging field of IP.
Basic new insights of IP include: a role for neuroinflammation in a spectrum of severe mental disorders, the consensus description of diagnosis and treatment of autoimmune psychosis (with outstanding clinical relevance), emerging findings of prevailing milder forms of neuroinflammation in severe mental disorders (SMD's) by emerging appropriate diagnostic methods (especially neuroimaging, CSF diagnostics), the role of environmental factors, especially infections, in the causality of SMD's. The interaction between genetic and environmental factors remains largely unresolved, with common pathophysiologic links possibly related to an IP constellation.
Access this article: https://doi.org/10.1016/j.jadr.2023.100656
