Role of ABT888, a Novel Poly(ADP-Ribose) Polymerase (PARP) Inhibitor in Countering Autophagy and Apoptotic Processes Associated to Spinal Cord Injury

Casili, Giovanna; Campolo, Michela; Lanza, Marika; Filippone, Alessia; Scuderi, Sarah Adriana; Ardizzone, Alessio; Esposito, Emanuela; Paterniti, Irene

doi:10.1007/s12035-020-02033-x

Cited by 28 publications

(22 citation statements)

References 77 publications

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“…The brain was rapidly removed and the ventral mesencephalon was isolated by dry dissection [56]. Tissues samples from brain were processed as previously described [57].…”

Section: Western Blot Analysismentioning

confidence: 99%

TLR7/8 in the Pathogenesis of Parkinson’s Disease

Campolo

Filippone

Biondo

et al. 2020

IJMS

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Neuroinflammation and autoimmune mechanisms have a key part in the pathogenesis of Parkinson’s disease (PD). Therefore, we evaluated the role of Toll-like receptors (TLRs) as a link between inflammation and autoimmunity in PD. An in vivo model of PD was performed by administration of 1-metil 4-fenil 1,2,3,6-tetraidro-piridina (MPTP) at the dose of 20 mg/kg every 2 h for a total administration of 80/kg, both in single Knock Out (KO) mice for TLR7, TLR 8, and TLR9 and in double KO mice for TLR 7/8-/-. All animals were compared with WT animals used as a control group. All animals were sacrificed after 7 days form the first administration of MPTP. The genetic absence of TLR 7 and 8 modified the PD pathway, increasing the immunoreactivity for TH and DAT compared to PD groups and decreasing microglia and astrocytes activation. Moreover, the deletion of TLR7 and TLR8 significantly reduced T-cell infiltration in the substantia nigra and lymph nodes, suggesting a reduction of T-cell activation. Therefore, our result highlights a possibility that an immunotherapy approach, by using a dual antagonist of TLR 7 and 8, could be considered as a possible target to develop new therapies for Parkinson diseases.

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“…The brain was rapidly removed and the ventral mesencephalon was isolated by dry dissection [56]. Tissues samples from brain were processed as previously described [57].…”

Section: Western Blot Analysismentioning

confidence: 99%

TLR7/8 in the Pathogenesis of Parkinson’s Disease

Campolo

Filippone

Biondo

et al. 2020

IJMS

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“…TUNEL was performed using a ‘Fluorescein In Situ Cell Death Detection Kit’ (Roche Diagnostics GmbH), according to the manufacturer's instructions, as previously described, 22 to define the level of intracerebral neuronal cell death.…”

Section: Methodsmentioning

confidence: 99%

The inhibition of mammalian target of rapamycin (mTOR) in improving inflammatory response after traumatic brain injury

Campolo

Casili

Lanza

et al. 2021

J Cellular Molecular Medi

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Traumatic brain injury (TBI) provokes primary and secondary damage on endothelium and brain parenchyma, leading neurons die rapidly by necrosis. The mammalian target of rapamycin signalling pathway (mTOR) manages numerous aspects of cellular growth, and it is up‐regulated after moderate to severe traumatic brain injury (TBI). Currently, the significance of this increased signalling event for the recovery of brain function is unclear; therefore, we used two different selective inhibitors of mTOR activity to discover the functional role of mTOR inhibition in a mouse model of TBI performed by a controlled cortical impact injury (CCI). Treatment with KU0063794, a dual mTORC1 and mTORC2 inhibitor, and with rapamycin as well‐known inhibitor of mTOR, was performed 1 and 4 hours subsequent to TBI. Results proved that mTOR inhibitors, especially KU0063794, significantly improved cognitive and motor recovery after TBI, reducing lesion volumes. Also, treatment with mTOR inhibitors ameliorated the neuroinflammation associated with TBI, showing a diminished neuronal death and astrogliosis after trauma. Our findings propose that the involvement of selective mTORC1/2 inhibitor may represent a therapeutic strategy to improve recovery after brain trauma.

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“…Histological evaluation was performed as previously described by Paterniti et al [49]. Tumor samples were quickly removed and fixed with 10% buffered formalin for at least 24 h at room temperature.…”

Section: Histological Evaluationmentioning

confidence: 99%

NLRP3 Inflammasome Inhibitor BAY-117082 Reduces Oral Squamous Cell Carcinoma Progression

Scuderi

Casili

Basilotta

et al. 2021

IJMS

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Oral cancer is one of the most common human malignancies, and its incidence is increasing worldwide. In particular, oral squamous cell carcinoma (OSCC) is characterized by high rates of proliferation, invasiveness, and metastasis. Currently, standard treatment for OSCC includes surgical removal, chemotherapy, and radiotherapy; however, the survival rate of patients with OSCC remains low, thus new therapies are needed. It has been proven that excessive NLRP3 inflammasome activation and apoptosis alteration may contribute to oral cancer progression. This study aimed to investigate the effect of BAY-117082, an NLRP3 inflammasome inhibitor, in an in vitro and in vivo xenograft model of oral cancer. In vitro results revealed that BAY-117082 at concentrations of 5, 10, and 30 µM was able to reduce OSCC cell viability. BAY-117082 at higher concentrations significantly reduced NLRP3, ASC, caspase-1, IL-1β, and IL-18 expression. Moreover, Bax, Bad, and p53 expression were increased, whereas Bcl-2 expression was reduced. Furthermore, the in vivo study demonstrated that BAY-117082 at doses of 2.5 and 5 mg/kg significantly decreased subcutaneous tumor mass, and also reduced NLRP3 inflammasome pathway activation. Therefore, based on these results, the use of BAY-117082 could be considered a promising strategy to counteract oral cancer progression, thanks its ability to modulate the NLRP3 inflammasome and apoptosis pathways.

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Role of ABT888, a Novel Poly(ADP-Ribose) Polymerase (PARP) Inhibitor in Countering Autophagy and Apoptotic Processes Associated to Spinal Cord Injury

Cited by 28 publications

References 77 publications

TLR7/8 in the Pathogenesis of Parkinson’s Disease

TLR7/8 in the Pathogenesis of Parkinson’s Disease

The inhibition of mammalian target of rapamycin (mTOR) in improving inflammatory response after traumatic brain injury

NLRP3 Inflammasome Inhibitor BAY-117082 Reduces Oral Squamous Cell Carcinoma Progression

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