The pro-apoptotic protein Bmf co-operates with Bim and Puma in neuron death induced by β-amyloid or NGF deprivation

Akhter, Rumana; Saleem, Suraiya; Saha, Anup Kumar; Biswas, Subhas C.

doi:10.1016/j.mcn.2018.02.011

Cited by 22 publications

(19 citation statements)

References 52 publications

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“…Interestingly, expression of Hrk/DP5, a neuronal specific BH3-only gene [117], follows a different pattern than the other BH3-only genes: largely absent during embryonic development, Hrk/DP5 expression is transiently induced at early postnatal stages and subsequently repressed in the mature brain [118], suggesting that it may have a unique function in the nervous system during that specific developmental period. Consistent with the observation that multiple BH3-only proteins are redundantly induced during apoptosis, the combined deletion or inhibition of multiple BH3-only genes is often needed to effectively block neuronal apoptosis [63,92,[119][120][121][122][123][124][125][126][127][128][129][130]. However, other stimuli such as those induced by arsenite exposure to cortical neurons can trigger the upregulation of a more restricted set of BH3-only where deletion of Puma alone can confer neuroprotection [131,132].…”

Section: Pro-apoptotic Bh3-only Proteinsmentioning

confidence: 72%

Apoptotic cell death regulation in neurons

2019

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Apoptosis plays a major role in shaping the developing nervous system during embryogenesis as neuronal precursors differentiate to become post‐mitotic neurons. However, once neurons are incorporated into functional circuits and become mature, they greatly restrict their capacity to die via apoptosis, thus allowing the mature nervous system to persist in a healthy and functional state throughout life. This robust restriction of the apoptotic pathway during neuronal differentiation and maturation is defined by multiple unique mechanisms that function to more precisely control and restrict the intrinsic apoptotic pathway. However, while these mechanisms are necessary for neuronal survival, mature neurons are still capable of activating the apoptotic pathway in certain pathological contexts. In this review, we highlight key mechanisms governing the survival of post‐mitotic neurons, while also detailing the physiological and pathological contexts in which neurons are capable of overcoming this high apoptotic threshold.

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Section: Pro-apoptotic Bh3-only Proteinsmentioning

confidence: 72%

Apoptotic cell death regulation in neurons

2019

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“…Atleast two major apoptotic pathways have been described in mammalian cells: the intrinsic pathway via Caspase-9 activation, in which death arises from mitochondrial dysfunction, and the extrinsic pathway via Caspase-8 activation, in which death is initiated from the activation of cell surface receptors. Bcl-2 family members play an important role in the intrinsic apoptotic pathway in several AD models (Paradis et al 1996, Akhter et al 2018 . The Bcl-2 family constitutes pro-survival (e.g.…”

Section: Introductionmentioning

confidence: 99%

TREM2 alters the phagocytic, apoptotic and inflammatory response to Aβ₄₂in HMC3 cells

Akhter

Shao

Formica

et al. 2020

Preprint

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Alzheimer’s disease (AD) is characterized by the accumulation in the brain of extracellular amyloid β (Aβ) plaques as well as intraneuronal inclusions (neurofibrillary tangles) consisting of total tau and phosphorylated tau. Also present are dystrophic neurites, loss of synapses, neuronal death, and gliosis. AD genetic studies have highlighted the importance of inflammation in this disease by identifying several risk associated immune response genes, including TREM2. TREM2 has been strongly implicated in basic microglia function including, phagocytosis, apoptosis, and the inflammatory response to Aβ in mouse brain and primary cells. These studies show that microglia are key players in the response to Aβ and in the accumulation of AD pathology. However, details are still missing about which apoptotic or inflammatory factors rely on TREM2 in their response to Aβ, especially in human cell lines. Given these previous findings our hypothesis is that TREM2 influences the response to Aβ toxicity by enhancing phagocytosis and inhibiting both the BCL-2 family of apoptotic proteins and pro-inflammatory cytokines. Aβ42 treatment of the human microglial cell line, HMC3 cells, was performed and TREM2 was overexpressed or silenced and the phagocytosis, apoptosis and inflammatory response were evaluated. Results indicate that a robust phagocytic response to Aβ after 24 hours requires TREM2 in HMC3 cells. Also, TREM2 inhibits Aβ induced apoptosis by activating the Mcl-1/Bim complex. TREM2 is involved in activation of IP-10, MIP-1a, and IL-8, while it inhibits FGF-2, VEGF and GRO. Taken together, TREM2 plays a role in enhancing the microglial functional response to Aβ toxicity in HMC3 cells. This novel information suggests that therapeutic strategies that seek to activate TREM2 may not only enhance phagocytosis, but it may also inhibit beneficial inflammatory factors, emphasizing the need to define TREM2-related inflammatory activity in not only mouse models of AD, but also in human AD.

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“…Cellular stress disintegrates a complex consisting of BMF and myosin V, causing the release of the proapoptotic factor. BMF then binds to the antiapoptotic agent Bcl2 and thereby initiates, among other factors, the mechanism of programmed cell death [78]. Otherwise, Bcl2 would interfere with the proapoptotic Bax and prevent an initiation of apoptosis [79].…”

Section: Introductionmentioning

confidence: 99%

Deregulated miR-29b-3p Correlates with Tissue-Specific Activation of Intrinsic Apoptosis in An Animal Model of Amyotrophic Lateral Sclerosis

Klatt

Theis

Hahn

et al. 2019

Cells

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Amyotrophic lateral sclerosis (ALS) is one of the most common incurable motor neuron disorders in adults. The majority of all ALS cases occur sporadically (sALS). Symptoms of ALS are caused by a progressive degeneration of motor neurons located in the motor cortex and spinal cord. The question arises why motor neurons selectively degenerate in ALS, while other cells and systems appear to be spared the disease. Members of the intrinsic apoptotic pathway are frequent targets of altered microRNA expression. Therefore, microRNAs and their effects on cell survival are subject of controversial debates. In this study, we investigated the expression of numerous members of the intrinsic apoptotic cascade by qPCR, western blot, and immunostaining in two different regions of the CNS of wobbler mice. Further we addressed the expression of miR-29b-3p targeting BMF, Bax, and, Bak, members of the apoptotic pathway. We show a tissue-specific differential expression of BMF, Bax, and cleaved-Caspase 3 in wobbler mice. An opposing regulation of miR-29b-3p expression in the cerebellum and cervical spinal cord of wobbler mice suggests different mechanisms regulating the intrinsic apoptotic pathway. Based on our findings, it could be speculated that miR-29b-3p might regulate antiapoptotic survival mechanisms in CNS areas that are not affected by neurodegeneration in the wobbler mouse ALS model.

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The pro-apoptotic protein Bmf co-operates with Bim and Puma in neuron death induced by β-amyloid or NGF deprivation

Cited by 22 publications

References 52 publications

Apoptotic cell death regulation in neurons

Apoptotic cell death regulation in neurons

TREM2 alters the phagocytic, apoptotic and inflammatory response to Aβ₄₂in HMC3 cells

Deregulated miR-29b-3p Correlates with Tissue-Specific Activation of Intrinsic Apoptosis in An Animal Model of Amyotrophic Lateral Sclerosis

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The pro-apoptotic protein Bmf co-operates with Bim and Puma in neuron death induced by β-amyloid or NGF deprivation

Cited by 22 publications

References 52 publications

Apoptotic cell death regulation in neurons

Apoptotic cell death regulation in neurons

TREM2 alters the phagocytic, apoptotic and inflammatory response to Aβ42in HMC3 cells

Deregulated miR-29b-3p Correlates with Tissue-Specific Activation of Intrinsic Apoptosis in An Animal Model of Amyotrophic Lateral Sclerosis

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TREM2 alters the phagocytic, apoptotic and inflammatory response to Aβ₄₂in HMC3 cells