Bcl-xl-Specific antibody labels activated microglia associated with Alzheimer's disease and other pathological states

Drache, B.; Diehl, Gretchen E.; Beyreuther, Konrad; Perlmutter, Lynn S.; König, Gerhard

doi:10.1002/(sici)1097-4547(19970101)47:1<98::aid-jnr11>3.0.co;2-6

Cited by 47 publications

(15 citation statements)

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“…Bcl-xL expression levels have been found to be high prior to birth, undetectable in neonatal tissue, low in young adult brain, and elevated again in the human aged brain [119], while over-expression of Bcl2 prevents neomycin-induced hearing loss in adult mouse [120]. Our findings showing the higher expressions of Bcl-xL and Bcl2 in aged mice are consistent with these previous findings and suggest protective effects of these genes during cochlear aging.…”

Section: Discussionsupporting

confidence: 90%

Apoptosis-related genes change their expression with age and hearing loss in the mouse cochlea

et al. 2008

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To understand possible causative roles of apoptosis gene regulation in age-related hearing loss (presbycusis), apoptotic gene expression patterns in the CBA mouse cochlea of four different age and hearing loss groups were compared, using GeneChip and real-time (qPCR) microarrays. GeneChip transcriptional expression patterns of 318 apoptosis-related genes were analyzed. Thirty eight probes (35 genes) showed significant differences in expression. The significant gene families include Caspases, B-cell leukemia/lymphoma2 family, P53, Cal-pains, Mitogen activated protein kinase family, Jun oncogene, Nuclear factor of kappa light chain gene enhancer in B-cells inhibitorrelated and tumor necrosis factor-related genes. The GeneChip results of 31 genes were validated using the new TaqMan ® Low Density Array (TLDA). Eight genes showed highly correlated results with the GeneChip data. These genes are: activating transcription factor3, B-cell leukemia/ lymphoma2, Bcl2-like1, caspase4 apoptosis-related cysteine protease 4, Calpain2, dual specificity phosphatase9, tumor necrosis factor receptor superfamily member12a, and Tumor necrosis factor superfamily member13b, suggesting they may play critical roles in inner ear aging.

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Section: Discussionsupporting

confidence: 90%

Apoptosis-related genes change their expression with age and hearing loss in the mouse cochlea

et al. 2008

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“…ASH-WEX- and FIV-mediated induction of apoptosis may be the result of inhibition of anti-apoptotic protein Bcl-xl. Upregulated Bcl-xl expression has been detected in reactive microglia of the patient with neurodegenerative diseases [60]. Both the extracts were also seen to elevate the levels of the PARP expression, whose cleavage into 27 and 87 kDa fragments leads to the apoptosis progression.…”

Section: Discussionmentioning

confidence: 99%

Aqueous extract from the Withania somnifera leaves as a potential anti-neuroinflammatory agent: a mechanistic study

Gupta

Kaur

2016

J Neuroinflammation

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BackgroundMicroglial-mediated neuroinflammation is a key factor underlying the pathogenesis of various neurodegenerative diseases and also an important target for the development of the neuroinflammation-targeted therapeutics. Conventionally, the nonsteroidal anti-inflammatory drugs (NSAIDs) are prescribed, but they are associated with long-term potential risks. Natural products are the cornerstone of modern therapeutics, and Ashwagandha is one such plant which is well known for its immunomodulatory properties in Ayurveda.MethodsThe current study was aimed to investigate the anti-neuroinflammatory potential of Ashwagandha (Withania somnifera) leaf water extract (ASH-WEX) and one of its active chloroform fraction (fraction IV (FIV)) using β-amyloid and lipopolysaccharide (LPS)-stimulated primary microglial cells and BV-2 microglial cell line. Iba-1 and α-tubulin immunocytochemistry was done to study the LPS- and β-amyloid-induced morphological changes in microglial cells. Inflammatory molecules (NFkB, AP1), oxidative stress proteins (HSP 70, mortalin), apoptotic markers (Bcl-xl, PARP), cell cycle regulatory proteins (PCNA, Cyclin D1), and MHC II expression were analyzed by Western blotting. Mitotracker and CellRox Staining, Sandwich ELISA, and Gelatin Zymography were done to investigate ROS, pro-inflammatory cytokines, and matrix metalloproteinase production, respectively. Ashwagandha effect on microglial proliferation, migration, and its apoptosis-inducing potential was studied by cell cycle analysis, migration assay, and Annexin-V FITC assay, respectively.ResultsASH-WEX and FIV pretreatment was seen to suppress the proliferation of activated microglia by causing cell cycle arrest at Go/G1 and G2/M phase along with decrease in cell cycle regulatory protein expression such as PCNA and Cyclin D1. Inhibition of microglial activation was revealed by their morphology and downregulated expression of microglial activation markers like MHC II and Iba-1. Both the extracts attenuated the TNF-α, IL-1β, IL-6, RNS, and ROS production via downregulating the expression of inflammatory proteins like NFkB and AP1. ASH-WEX and FIV also restricted the migration of activated microglia by downregulating metalloproteinase expression. Controlled proliferation rate was also accompanied by apoptosis of activated microglia. ASH-WEX and FIV were screened and found to possess Withaferin A and Withanone as active phytochemicals.ConclusionsThe current data suggests that ASH-WEX and FIV inhibit microglial activation and migration and may prove to be a potential therapeutic candidate for the suppression of neuroinflammation in the treatment of neurodegenerative diseases.

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“…The Bcl-2 protein family consists of proapoptotic and antiapoptotic members that interact at both the physical and the functional levels to regulate mitochondrial integrity and apoptotic cell death [28]. Bcl-2 and Bax are regulated by the mitochondrial pathway, which are considered to be an important step in controlling and initiating apoptosis in AD [29]. In the present investigation, we demonstrated that FMJ enhanced the expression of the antiapoptotic protein Bcl-2 and decreased the expression of the proapoptotic protein Bax, thus resulting in a reduction of caspase activation.…”

Section: Discussionmentioning

confidence: 99%

Fumanjian, a Classic Chinese Herbal Formula, Can Ameliorate the Impairment of Spatial Learning and Memory through Apoptotic Signaling Pathway in the Hippocampus of Rats with Aβ_1–40‐Induced Alzheimer’s Disease

Cui

et al. 2014

Evidence-Based Complementary and Alternative Medicine

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Alzheimer's disease (AD) is the most common form of dementia and lacks disease-altering treatments. Fumanjian (FMJ), a famous classic Chinese herbal prescription for dementia, was first recorded in the Complete Works of Jingyue during the Ming Dynasty. This study aimed to investigate whether FMJ could prevent cognitive deficit and take neuroprotective effects in Aβ 1–40-induced rat model through apoptotic signaling pathway. AD model was established by bilateral injection of Aβ 1–40 into hippocampus in rat. All rats were tested for their capabilities of spatial navigation and memorization by Morris water maze. Apoptosis was tested using TUNEL staining in hippocampus neuronal cells; RT-PCR tested expression of Bcl-2 and Bax mRNA; western blotting tested protein level of cleaved caspase-3. After 14 days of treatment, FMJ significantly improved the escape latency and enhanced platform-cross number compared with the Aβ 1–40-injected group (P < 0.05 or P < 0.01). FMJ also significantly decreased number of TUNEL-positive neuronal apoptosis and the expressions of Bax and cleaved Caspase-3 and increased the expression of Bcl-2 (P < 0.01) compared with AD model group. In conclusion, FMJ exerts a protective effect against Aβ 1–40-induced learning and memory deficits and neuronal apoptosis, suggesting that FMJ could be used as a potential therapeutic formula for AD.

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Bcl-xl-Specific antibody labels activated microglia associated with Alzheimer's disease and other pathological states

Cited by 47 publications

References 40 publications

Apoptosis-related genes change their expression with age and hearing loss in the mouse cochlea

Apoptosis-related genes change their expression with age and hearing loss in the mouse cochlea

Aqueous extract from the Withania somnifera leaves as a potential anti-neuroinflammatory agent: a mechanistic study

Fumanjian, a Classic Chinese Herbal Formula, Can Ameliorate the Impairment of Spatial Learning and Memory through Apoptotic Signaling Pathway in the Hippocampus of Rats with Aβ_1–40‐Induced Alzheimer’s Disease

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Bcl-xl-Specific antibody labels activated microglia associated with Alzheimer's disease and other pathological states

Cited by 47 publications

References 40 publications

Apoptosis-related genes change their expression with age and hearing loss in the mouse cochlea

Apoptosis-related genes change their expression with age and hearing loss in the mouse cochlea

Aqueous extract from the Withania somnifera leaves as a potential anti-neuroinflammatory agent: a mechanistic study

Fumanjian, a Classic Chinese Herbal Formula, Can Ameliorate the Impairment of Spatial Learning and Memory through Apoptotic Signaling Pathway in the Hippocampus of Rats with Aβ1–40‐Induced Alzheimer’s Disease

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Fumanjian, a Classic Chinese Herbal Formula, Can Ameliorate the Impairment of Spatial Learning and Memory through Apoptotic Signaling Pathway in the Hippocampus of Rats with Aβ_1–40‐Induced Alzheimer’s Disease