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343 results on '"Prabhakar, Bellur S"'

2. Brain-immune interactions: implication for cognitive impairments in Alzheimer's disease and autoimmune disorders.

Author

Kadam, Rashmi, Gupta, Muskan, Lazarov, Orly, and Prabhakar, Bellur S

Subjects
ALZHEIMER'S disease, TYPE 1 diabetes, SYSTEMIC lupus erythematosus, AUTOIMMUNE diseases, NATURAL immunity
Abstract

Progressive memory loss and cognitive dysfunction, encompassing deficits in learning, memory, problem solving, spatial reasoning, and verbal expression, are characteristics of Alzheimer's disease and related dementia. A wealth of studies has described multiple roles of the immune system in the development or exacerbation of dementia. Individuals with autoimmune disorders can also develop cognitive dysfunction, a phenomenon termed "autoimmune dementia." Together, these findings underscore the pivotal role of the neuroimmune axis in both Alzheimer's disease and related dementia and autoimmune dementia. The dynamic interplay between adaptive and innate immunity, both in and outside the brain, significantly affects the etiology and progression of these conditions. Multidisciplinary research shows that cognitive dysfunction arises from a bidirectional relationship between the nervous and immune systems, though the specific mechanisms that drive cognitive impairments are not fully understood. Intriguingly, this reciprocal regulation occurs at multiple levels, where neuronal signals can modulate immune responses, and immune system–related processes can influence neuronal viability and function. In this review, we consider the implications of autoimmune responses in various autoimmune disorders and Alzheimer's disease and explore their effects on brain function. We also discuss the diverse cellular and molecular crosstalk between the brain and the immune system, as they may shed light on potential triggers of peripheral inflammation, their effect on the integrity of the blood-brain barrier, and brain function. Additionally, we assess challenges and possibilities associated with developing immune-based therapies for the treatment of cognitive decline. [ABSTRACT FROM AUTHOR]

Published
2024
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30. Immune Tolerance in Autoimmune Central Nervous System Disorders

Author

Jayaraman, Sundararajan and Prabhakar, Bellur S.

Subjects
Proteolipid protein, Tumor necrosis factor-α, Tolerance, Human leukocyte antigen, Autoimmune diseases, T regulatory cells, GM-CSF, Neuromyelitis optica, Article, Multiple sclerosis, Th1, Myelin basic protein, Cerebrospinal fluid, Myelin oligodendrocyte glycoprotein, Central nervous system, Anergy, Foxp3, Interleukin 17, Trichostatin A, Interferon-γ, Th17, Blood-brain barrier
Abstract

Multiple sclerosis (MS) afflicts genetically predisposed individuals and is associated with T lymphocyte-mediated damage to the myelin sheath of neurons in the central nervous system, resulting in severely impaired signal transmission. The mechanisms of the induction and manifestation of MS are not entirely understood. The control of autoimmune disorders is accomplished by both central tolerance in which autoreactive T lymphocytes are eliminated in the thymus and by tolerance mechanisms that operate in the periphery. Among the many mechanisms described, T regulatory (Treg) cells derived from the thymus (tTregs) and induced (iTregs) in the periphery as well as T regulatory type 1 cells (Tr1) are involved in many disease models. However, the precise details of the generation and perpetuation of these various Treg subsets and their relevance to the regulation of autoimmune diseases remain elusive. In this review, we critically analyze the current knowledge of the tolerance mechanisms involved in the regulation of MS and its animal model, experimental autoimmune encephalomyelitis.

Published
2019

39. A noncovalent class of papain-like protease/ deubiquitinase inhibitors blocks SARS virus replication

Author

Ratia, Kiira, Pegan, Scott, Takayama, Jun, Sleeman, Katrina, Coughlin, Melissa, Baliji, Surendranath, Chaudhuri, Rima, Fu, Wentao, Prabhakar, Bellur S., Johnson, Michael E., Baker, Susan C., Ghosh, Arun K., and Mesecar, Andrew D.

Subjects
Severe acute respiratory syndrome -- Drug therapy, Proteases -- Health aspects, Science and technology
Abstract

We report the discovery and optimization of a potent inhibitor against the papain-like protease (PLpro) from the coronavirus that causes severe acute respiratory syndrome (SARS-CoV). This unique protease is not only responsible for processing the viral polyprotein into its functional units but is also capable of cleaving ubiquitin and ISG15 conjugates and plays a significant role in helping SARS-CoV evade the human immune system. We screened a structurally diverse library of 50,080 compounds for inhibitors of PLpro and discovered a noncovalent lead inhibitor with an [IC.sub.50] value of 20 [micro]M, which was improved to 600 nM via synthetic optimization. The resulting compound, GRL0617, inhibited SARS-CoV viral replication in Vero E6 cells with an [EC.sub.50] of 15 [micro]M and had no associated cytotoxicity. The X-ray structure of PLpro in complex with GRL0617 indicates that the compound has a unique mode of inhibition whereby it binds within the S4-S3 subsites of the enzyme and induces a loop closure that shuts down catalysis at the active site. These findings provide proof-of-principle that PLpro is a viable target for development of antivirals directed against SARS-CoV, and that potent noncovalent cysteine protease inhibitors can be developed with specificity directed toward pathogenic deubiquitinating enzymes without inhibiting host DUBs. ubiquitin-specific protease | noncovalent cysteine protease inhibitor | severe acute respiratory syndrome antiviral | X-ray structure

Published
2008

48. Type 2 Deiodinase and Host Responses of Sepsis and Acute Lung Injury

Author

Ma, Shwu-Fan, Xie, Lishi, Pino-Yanes, Maria, Sammani, Saad, Wade, Michael S., Letsiou, Eleftheria, Siegler, Jessica, Wang, Ting, Infusino, Giovanni, Kittles, Rick A., Flores, Carlos, Zhou, Tong, Prabhakar, Bellur S., Moreno-Vinasco, Liliana, Villar, Jesus, Jacobson, Jeffrey R., Dudek, Steven M., and Garcia, Joe G. N.

Published
2011
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