Impact of aging immune system on neurodegeneration and potential immunotherapies

Liang, Zhanfeng; Zhao, Yang; Ruan, Linhui; Zhu, Linnan; Jin, Kunlin; Zhuge, Qichuan; Su, Dong Ming; Zhao, Yong

doi:10.1016/j.pneurobio.2017.07.006

Cited by 39 publications

(45 citation statements)

References 409 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The motor symptoms are generally considered the consequence of the loss of dopaminergic neurons in the substantia nigra pars compacta of the midbrain. The main pathological hallmark of PD is the deposition of an intracellular fibrillar and misfolded protein named α‐synuclein (Lewy bodies) causing a complex immunopathogenic response leading to PD . The etiology of the disease is still unknown; several studies in disease animal models suggest that PD could be a T‐cell‐dependent autoimmunity associated with neuronal death.…”

Section: Pathological Significance Of Senescence In the Brainmentioning

confidence: 99%

“…It has been demonstrated that CD4+ T cell expressing altered levels of the dopamine receptor D3 favors acquisition of the Th1 inflammatory phenotype, whereas other authors proposed that T cells specific for the neuromelanin can activate neuromelanin‐specific B cells leading to the production of autoantibody. In any case, stimulated T cells are able to infiltrate into the brain and activate resting microglia and astrocytes, finally causing neuroinflammation. On the other hand, microglia are able to recognize and phagocytize extracellular α‐synuclein aggregates and are also activated by neuronal cell death itself.…”

Section: Pathological Significance Of Senescence In the Brainmentioning

confidence: 99%

See 1 more Smart Citation

Innate immunity and cellular senescence: The good and the bad in the developmental and aged brain

Spinelli

Martucciello

Nori

et al. 2018

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Ongoing studies evidence cellular senescence in undifferentiated and specialized cells from tissues of all ages. Although it is believed that senescence plays a wider role in several stress responses in the mature age, its participation in certain physiological and pathological processes throughout life is coming to light. The "senescence machinery" has been observed in all brain cell populations, including components of innate immunity (e.g., microglia and astrocytes). As the beneficial versus detrimental implications of senescence is an open question, we aimed to analyze the contribution of immune responses in regulatory mechanisms governing its distinct functions in healthy (development, organogenesis, danger patrolling events) and diseased brain (glioma, neuroinflammation, neurodeneration), and the putative connection between cellular and molecular events governing the 2 states. Particularly this review offers new insights into the complex roles of senescence both as a chronological event as age advances, and as a molecular mechanism of brain homeostasis through the important contribution of innate immune responses and their crosstalk with neighboring cells in brain parenchyma. We also highlight the impact of the recently described glymphatic system and brain lymphatic vasculature in the interplay between peripheral and central immune surveillance and its potential implication during aging. This will open new ways to understand brain development, its deterioration during aging, and the occurrence of several oncological and neurodegenerative diseases.

show abstract

Section: Pathological Significance Of Senescence In the Brainmentioning

confidence: 99%

Section: Pathological Significance Of Senescence In the Brainmentioning

confidence: 99%

Innate immunity and cellular senescence: The good and the bad in the developmental and aged brain

Spinelli

Martucciello

Nori

et al. 2018

Journal of Leukocyte Biology

View full text Add to dashboard Cite

show abstract

“…CD8+ subset presence during the time negatively impacts the immune system also in healthy CMV-infected individuals [ 66 ]. These alterations result in the impaired cellular immune response in infections and vaccinations [ 67 ].…”

Section: Immunosenescence Of Adaptive Immune Response Cellsmentioning

confidence: 99%

“…The effects of aging refer to the physiological changes of neuronal and nonneuronal cells [ 104 ], including progressive degeneration and loss of DA neurons in the midbrain substantia nigra, reduction of nigral pigmented neurons, accumulation of alpha-synuclein, and the inhibition of the UPS (ubiquitin proteasome system) [ 109 ]. The accumulation of α -synuclein leads to lamellated eosinophilic cytoplasmic inclusions, called “Lewy bodies” in the neuronal body, and to the insoluble polymers (Lewy neurites) in neuronal processes, astrocytes, and oligodendroglial cells [ 104 , 67 ].…”

Section: Immunosenescence and Inflamm-aging In Neurodegenerative Dmentioning

confidence: 99%

The Role of Immunosenescence in Neurodegenerative Diseases

Costantini

D’Angelo

Reale

2018

Mediators of Inflammation

View full text Add to dashboard Cite

Aging is characterized by the progressive decline of physiological function and tissue homeostasis leading to increased vulnerability, degeneration, and death. Aging-related changes of the innate and adaptive immune system include decline in the preservation and enhancement of many immune functions, such as changes in the number of circulating monocytic and dendritic cells, thymic involution, T cell polyfunctionality, or production of proinflammatory cytokines, and are defined as immunosenescence. Inflammatory functions are increased with age, causing the chronic low-grade inflammation, referred to as inflamm-aging, that contribute, together with immunosenescence, to neurodegenerative diseases. In this review, we discuss the link between the immune and nervous systems and how the immunosenescence and inflamm-aging can contribute to neurodegenerative diseases.

show abstract

“…Indeed, several studies reported that apparently healthy humans present a chronic low-level of inflammation associated with aging, a phenomenon known as “inflammaging” (a contraction of inflammation and aging) 114 . Although still not fully understood, the impact of chronic inflammation on brain functions is suspected to be deleterious and to favor the progression of cognitive impairment associated with aging 115 . Interestingly, MPIO-αVCAM-1 revealed a significant activation of the cerebrovasculature in otherwise healthy, aged mice 29 , 43 .…”

Section: Molecular Mri Of Endothelial Activation In Neurodegenerativementioning

confidence: 99%

Molecular Magnetic Resonance Imaging of Endothelial Activation in the Central Nervous System

et al. 2018

View full text Add to dashboard Cite

Endothelial cells of the central nervous system over-express surface proteins during neurological disorders, either as a cause, or a consequence, of the disease. Since the cerebral vasculature is easily accessible by large contrast-carrying particles, it constitutes a target of choice for molecular magnetic resonance imaging (MRI). In this review, we highlight the most recent advances in molecular MRI of brain endothelial activation and focus on the development of micro-sized particles of iron oxide (MPIO) targeting adhesion molecules including intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), P-Selectin and E-Selectin. We also discuss the perspectives and challenges for the clinical application of this technology in neurovascular disorders (ischemic stroke, intracranial hemorrhage, subarachnoid hemorrhage, diabetes mellitus), neuroinflammatory disorders (multiple sclerosis, brain infectious diseases, sepsis), neurodegenerative disorders (Alzheimer's disease, vascular dementia, aging) and brain cancers (primitive neoplasms, metastasis).

show abstract

Impact of aging immune system on neurodegeneration and potential immunotherapies

Cited by 39 publications

References 409 publications

Innate immunity and cellular senescence: The good and the bad in the developmental and aged brain

Innate immunity and cellular senescence: The good and the bad in the developmental and aged brain

The Role of Immunosenescence in Neurodegenerative Diseases

Molecular Magnetic Resonance Imaging of Endothelial Activation in the Central Nervous System

Contact Info

Product

Resources

About