Neuroscience
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The pervasive reach of the inflammatory system is evidenced by its involvement in numerous disease states. Cardiovascular disease, marked by high levels of circulating inflammatory mediators, affects an estimated 83.6 million Americans. Similarly, human immunodeficiency virus (HIV) produces a paradoxical state of generalized immune activity despite widespread immunosuppression, and affects 35 million people worldwide. ⋯ In this combined disease state, immune mechanisms that are common to both CVD and HIV may interact to generate a progressive condition that contributes to the exacerbated pathogenesis of the other to the net effect of damage to the brain. In this review, we will outline inflammatory cell mediators that promote cardiovascular risk factors and disease initiation and detail how HIV-related proteins may accelerate this process. Finally, we examine the extent to which these comorbid conditions act as parallel, perpendicular, or progressive sequela of events to generate a neurodegenerative environment, and consider potential strategies that can be implemented to reduce the burden of CVD and inflammation in PLWH.
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Neuroinflammation has long been known as an accompanying pathology of Alzheimer's disease. Microglia surrounding amyloid plaques in the brain of Auguste D were described in the original publication of Alois Alzheimer. ⋯ While gaps in our knowledge remain, and conflicting data are abound in the field, our understanding of the complexities and heterogeneous functions of the inflammatory response in Alzheimer's is vastly improved. This review article will discuss some of the roles of neuroinflammation in Alzheimer's disease, in particular, how understanding heterogeneity in the individual inflammatory response can be used in therapeutic development and as a mechanism of personalizing our treatment of the disease.
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Microglia play major roles in initiation, coordination and execution of innate immunity in the brain. In the adult brain, these include maintenance of homeostasis, neuron and tissue repair, and eliminating infectious agents, apoptotic cells, and misfolded proteins. Some of these activities are accompanied by inflammatory reactions; and others are performed with no inflammatory effects. ⋯ The defects in the intramembrane cleavage result in dysfunction of phagocytosis signaling. The association of TREM2 mutations with neurodegenerative disease also calls for the understanding of the biology and pathological role of non-mutated TREM2 on human brains and microglia. This review provides a summary of current literature in TREM2 and DAP12 from several aspects, and proposes a theory that loss of TREM2 functions might contribute to the immunopathogenic role of microglia in Alzheimer's disease.
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Peripheral nerves regenerate following injury due to the effective activation of the intrinsic growth capacity of the neurons and the formation of a permissive pathway for outgrowth due to Wallerian degeneration (WD). WD and subsequent regeneration are significantly influenced by various immune cells and the cytokines they secrete. Although macrophages have long been known to play a vital role in the degenerative process, recent work has pointed to their importance in influencing the regenerative capacity of peripheral neurons. In this review, we focus on the various immune cells, cytokines, and chemokines that make regeneration possible in the peripheral nervous system, with specific attention placed on the role macrophages play in this process.
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Recent research suggests a complex role for microglia not only in Parkinson's disease but in other disorders involving alpha-synuclein aggregation, such as multiple system atrophy. In these neurodegenerative processes, the activation of microglia is a common pathological finding, which disturbs the homeostasis of the neuronal environment otherwise maintained, among others, by microglia. The term activation comprises any deviation from what otherwise is considered normal microglia status, including cellular abundance, morphology or protein expression. ⋯ Microglia's behavior will therefore be a determinant on the disease's progression. For this reason we believe that the better understanding of microglia's response to alpha-synuclein pathological accumulation across brain areas and disease stages is essential to develop novel therapeutic tools for Parkinson's disease and other alpha-synucleinopathies. In this review we will revise the most recent findings and developments with regard to alpha-synuclein and microglia in Parkinson's disease.