The neuroprotective effects of β-hydroxybutyrate on Aβ-injected rat hippocampus in vivo and in Aβ-treated PC-12 cells in vitro

Xie, Guanghong; Tian, Wei; Teng, Wei; Liu, Fangmeng

doi:10.3109/10715762.2014.987274

Cited by 48 publications

(31 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Experiments showed that BHB decreased K + efflux and endoplasmic reticulum stress (Youm et al, 2015; Bae et al, 2016). Furthermore, BHB is transported to brain parenchyma and plays a neuroprotective role under several pathological conditions (Orhan et al, 2015; Xie et al, 2015). …”

Section: Targeting the Nlrp3 Inflammasome For The Treatment Of Neurolmentioning

confidence: 99%

NLRP3 Inflammasome in Neurological Diseases, from Functions to Therapies

Song

Pei

Yao

et al. 2017

Front. Cell. Neurosci.

353

275

View full text Add to dashboard Cite

Neuroinflammation has been identified as a causative factor of multiple neurological diseases. The nucleotide-binding oligomerization domain-, leucine-rich repeat- and pyrin domain-containing 3 (NLRP3) inflammasome, a subcellular multiprotein complex that is abundantly expressed in the central nervous system (CNS), can sense and be activated by a wide range of exogenous and endogenous stimuli such as microbes, aggregated and misfolded proteins, and adenosine triphosphate, which results in activation of caspase-1. Activated caspase-1 subsequently leads to the processing of interleukin-1β (IL-1β) and interleukin-18 (IL-18) pro-inflammatory cytokines and mediates rapid cell death. IL-1β and IL-18 drive inflammatory responses through diverse downstream signaling pathways, leading to neuronal damage. Thus, the NLRP3 inflammasome is considered a key contributor to the development of neuroinflammation. In this review article, we briefly discuss the structure and activation the NLRP3 inflammasome and address the involvement of the NLRP3 inflammasome in several neurological disorders, such as brain infection, acute brain injury and neurodegenerative diseases. In addition, we review a series of promising therapeutic approaches that target the NLRP3 inflammasome signaling including anti-IL-1 therapy, small molecule NLRP3 inhibitors and other compounds, however, these approaches are still experimental in neurological diseases. At present, it is plausible to generate cell-specific conditional NLRP3 knockout (KO) mice via the Cre system to investigate the role of the NLRP3 inflammasome, which may be instrumental in the development of novel pharmacologic investigations for neuroinflammation-associated diseases.

show abstract

Section: Targeting the Nlrp3 Inflammasome For The Treatment Of Neurolmentioning

confidence: 99%

NLRP3 Inflammasome in Neurological Diseases, from Functions to Therapies

Song

Pei

Yao

et al. 2017

Front. Cell. Neurosci.

353

275

View full text Add to dashboard Cite

show abstract

“…BHB disrupted ASC oligomerization and speck formation, prevented K + efflux, and reduced endoplasmic reticulum (ER) stress. Moreover, BHB crossed the BBB and had a neuroprotective effect in an animal model of Aβ‐induced neurodegeneration and traumatic brain injury (Supplemental Table) …”

Section: Nlrp3 Inflammasome‐mediated Inflammatory Pathways In Pdmentioning

confidence: 99%

Targeting the Microglial NLRP3 Inflammasome and Its Role in Parkinson's Disease

et al. 2019

View full text Add to dashboard Cite

Excessive activation of microglia and subsequent release of proinflammatory cytokines play a crucial role in neuroinflammation and neurodegeneration in Parkinson's disease (PD). Components of the nucleotide‐binding oligomerization domain and leucine‐rich‐repeat‐ and pyrin‐domain‐containing 3 inflammasome complex, leucine‐rich‐repeat‐ and pyrin‐domain‐containing 3, caspase‐1, and apoptosis‐associated speck‐like protein containing a CARD, are highly expressed in activated microglia in PD patient brains. Findings suggest that neurotoxins, aggregation of α‐synuclein, mitochondrial reactive oxygen species, and disrupted mitophagy are the key regulators of microglial leucine‐rich‐repeat‐ and pyrin‐domain‐containing 3 inflammasome activation and release of interleukin‐1β and interleukin‐18 caspase‐1‐mediated pyroptotic cell death in the substantia nigra of the brain. Although this evidence suggests the leucine‐rich‐repeat‐ and pyrin‐domain‐containing 3 inflammasome may be a potential drug target for treatment of PD, the exact mechanism of how the microglia sense these stimuli and initiate leucine‐rich‐repeat‐ and pyrin‐domain‐containing 3 inflammasome signaling is unknown. Here, the molecular mechanism and regulation of microglial leucine‐rich‐repeat‐ and pyrin‐domain‐containing 3 inflammasome activation and its role in the pathogenesis of PD are discussed. Moreover, the potential of both endogenous and synthetic leucine‐rich‐repeat‐ and pyrin‐domain‐containing 3 inflammasome modulators, long noncoding RNA, microRNA to develop novel therapeutics to treat PD is presented. Overall, we recommend that the microglial leucine‐rich‐repeat‐ and pyrin‐domain‐containing 3 inflammasome can be a potential target for PD treatment. © 2019 International Parkinson and Movement Disorder Society

show abstract

“…A number of recent papers have used what they refer to as an acute model of AD by directly injecting Aβ(1–40) or Aβ(1-42) into the hippocampus. When compounds were administered prior to the injection of Aβ, beneficial effects were noted for SuHeXiang essential oil [89], sulforaphane [90, 91], β-hydoxybutyrate [92], orientin [93], and baicalin [94]. A major caveat to all the studies discussed in this section is that none of them were done in Nrf2−/− or knockdown mice to clearly demonstrate that these same compounds being tested require Nrf2 for their therapeutic effects.…”

Section: Nrf2 In Alzheimer's Diseasementioning

confidence: 99%

Nrf2—a therapeutic target for the treatment of neurodegenerative diseases

Johnson

2015

Free Radical Biology and Medicine

277

228

View full text Add to dashboard Cite

The brain is very sensitive to changes in redox status; thus maintaining redox homeostasis in the brain is critical for the prevention of accumulating oxidative damage. Aging is the primary risk factor for developing neurodegenerative diseases. In addition to age, genetic and environmental risk factors have also been associated with disease development. The primary reactive insults associated with the aging process are a result of oxidative stress (OS) and nitrosative stress (NS). Markers of increased oxidative stress, protein and DNA modification, inflammation, and dysfunctional proteostasis have all been implicated in contributing to the progression of neurodegeneration. The ability of the cell to combat OS/NS and maintain a clearance mechanism for misfolded aggregating proteins determines whether or not it will survive. A critical pathway in this regard is the Nrf2 (nuclear factor erythroid 2-related factor 2)- antioxidant response element (ARE) pathway. Nrf2 activation has been shown to mitigate a number of pathologic mechanisms associated with Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. This review will focus on the role of Nrf2 in these diseases and the potential for Nrf2 activation to mitigate disease progression.

show abstract

The neuroprotective effects of β-hydroxybutyrate on Aβ-injected rat hippocampus in vivo and in Aβ-treated PC-12 cells in vitro

Cited by 48 publications

References 62 publications

NLRP3 Inflammasome in Neurological Diseases, from Functions to Therapies

NLRP3 Inflammasome in Neurological Diseases, from Functions to Therapies

Targeting the Microglial NLRP3 Inflammasome and Its Role in Parkinson's Disease

Nrf2—a therapeutic target for the treatment of neurodegenerative diseases

Contact Info

Product

Resources

About