Tetracyclines and Neuromuscular Disorders

Orsucci, Daniele; Mancuso, Michelangelo; Filosto, Massimiliano; Siciliano, Gabriele

doi:10.2174/157015912800604498

Cited by 21 publications

(13 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Adenosine phosphate (enrichment score = 0.734 and p -value = 9.83 × 10 −3 ) is involved in adenosine homeostasis that may reportedly play important roles in ALS progression [ 45 ]. Tetracycline (enrichment score = 0.673 and p -value = 9.75 × 10 −3 ) is reportedly one of the antibiotics that could act as neuroprotective molecules in neurological diseases such as Huntington’s disease, Parkinson’s disease, stroke, and multiple sclerosis [ 46 ]. A previous study mentioned that phentolamine (enrichment score = 0.611 and p -value = 4.59 × 10 −3 ) was effective to reduce blood pressure in a patient with ALS [ 47 ].…”

Section: Resultsmentioning

confidence: 99%

An Integrative Transcriptome-Wide Analysis of Amyotrophic Lateral Sclerosis for the Identification of Potential Genetic Markers and Drug Candidates

Park

Kim

Song

et al. 2021

IJMS

View full text Add to dashboard Cite

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative neuromuscular disease. Although genome-wide association studies (GWAS) have successfully identified many variants significantly associated with ALS, it is still difficult to characterize the underlying biological mechanisms inducing ALS. In this study, we performed a transcriptome-wide association study (TWAS) to identify disease-specific genes in ALS. Using the largest ALS GWAS summary statistic (n = 80,610), we identified seven novel genes using 19 tissue reference panels. We conducted a conditional analysis to verify the genes’ independence and to confirm that they are driven by genetically regulated expressions. Furthermore, we performed a TWAS-based enrichment analysis to highlight the association of important biological pathways, one in each of the four tissue reference panels. Finally, utilizing a connectivity map, a database of human cell expression profiles cultured with bioactive small molecules, we discovered functional associations between genes and drugs to identify 15 bioactive small molecules as potential drug candidates for ALS. We believe that, by integrating the largest ALS GWAS summary statistic with gene expression to identify new risk loci and causal genes, our study provides strong candidates for molecular basis experiments in ALS.

show abstract

Section: Resultsmentioning

confidence: 99%

An Integrative Transcriptome-Wide Analysis of Amyotrophic Lateral Sclerosis for the Identification of Potential Genetic Markers and Drug Candidates

Park

Kim

Song

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…In spite of being antibiotics, tetracyclines including minocycline can act as neuroprotective agents in several neurological disorders such as Parkinson disease, Huntington disease et al . through inhibiting microglial activation, apoptosis and ROS production 37 – 40 . Minocycline has also been proposed to be a potential neuroprotectant against radiation-induced damage 41 .…”

Section: Discussionmentioning

confidence: 99%

The inhibitory effect of minocycline on radiation-induced neuronal apoptosis via AMPKα1 signaling-mediated autophagy

Zhang¹,

Huang²,

Chen³

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Due to an increasing concern about radiation-induced cognitive deficits for brain tumor patients receiving radiation therapy, developing and evaluating countermeasures has become inevitable. Our previous study has found that minocycline, a clinical available antibiotics that can easily cross the blood brain barrier, mitigates radiation-induced long-term memory loss in rats, accompanied by decreased hippocampal neuron apoptosis. Thus, in the present study, we report an unknown mechanism underlying the neuroprotective effect of minocycline. We demonstrated that minocycline prevented primary neurons from radiation-induced apoptosis and promoted radiation-induced autophagy in vitro. Moreover, using an immortalized mouse hippocampal neuronal cell line, HT22 cells, we found that the protective effect of minocycline on irradiated HT22 cells was not related to DNA damage repair since minocycline did not facilitate DNA DSB repair in irradiated HT22 cells. Further investigation showed that minocycline significantly enhanced X-irradiation-induced AMPKα1 activation and autophagy, thus resulting in decreased apoptosis. Additionally, although the antioxidant potential of minocycline might contribute to its apoptosis-inhibitory effect, it was not involved in its enhancive effect on radiation-induced AMPKα1-mediated autophagy. Taken together, we have revealed a novel mechanism for the protective effect of minocycline on irradiated neurons, e.g. minocycline protects neurons from radiation-induced apoptosis via enhancing radiation-induced AMPKα1-mediated autophagy.

show abstract

“…Minosiklinin etkili olduğu savunulan diğer bir durum ise Parkinson hastalığıdır [48] . İn vitro olarak gliyal [indüklenebilir nitrik oksit (NO) (İNOS) sentaz] ekspresyonunu dolaylı inhibe ederken, NO aracılı nörotoksisiteyi direkt olarak inhibe ederek MPTP (1-metil-4-fenil-1,2,3,6-tetrahidropirin) fare modelinde Parkinson hastalığındaki nigrostriatal dopaminerjik nöron dejenerasyonunu önlediği gösterilmiştir [27,49] .…”

Section: Nöroprotektif Etkiunclassified

Non Antimicrobial Effects of Antibacterial Agents

Demiraslan¹,

Uysal²

2018

mjima

View full text Add to dashboard Cite

Aside from their antibacterial activity, antimicrobial agents have also some beneficial effects due to their chemical structures. These effects include anti-inflammatory, immunomodulatory, anti-cancer, anti-angiogenic, neuroprotective, cardioprotective, augmented gastrointestinal motility, and binding toxins. This paper does not comprise non-antimicrobial effects of all antibiotics due to the fact that the issue is very extended. We reviewed use of penicillins in mushroom poisoning and their promising inhibitor effect on proliferation of cervical carcinoma and leukemia cells. We summarized neuroprotective effect of ceftriaxone and its inhibitory potential on proliferation of lung cancer cells. Tetracyclines are agents that have been focused on and investigated for a long time, and demeclocycline that belongs to this group is used for inappropriate antidiuretic hormone secretion. Moreover, low-dose doxycycline that is also a tetracycline, has been approved for the treatment of periodontitis, and inhibition of matrix metalloproteinase enzyme is the responsible mechanism for its anti-inflammatory action. Matrix metalloproteinase inhibition also provides a decrease in tumor angiogenesis and metastasis. Minocycline, another tetracycline, reduces the synthesis of beta-amyloid which plays a key role in Alzheimer's disease and other neurodegenerative diseases, and it also inhibits glial inducible nitric oxide (NO) synthase and NOmediated neurotoxicity. Erythromycin that is a macrolide antibiotic is used as a gastrointestinal motility augmenter; azithromycin gives an early improvement in patients with cystic fibrosis due to its anti-inflammatory effect. It has been shown that clarithromycin decreases the metastatic AbstractAntimikrobiyal ajanlar kimyasal yapılarından dolayı bakterilere karşı aktiviteleri dışında bazı yararlı etkilere de sahiptirler. Bunlar arasında antienflamatuvar, immünomodülatör, anti-kanser, anti-anjiyogenik, nöroprotektif, kardiyoprotektif, gastrointestinal hareket artırıcı ve toksin bağlayıcı etkiler sayılabilir. Bu yazıda, konu çok geniş olduğundan dolayı sınırlı sayıda antibiyotiğin antimikrobiyal dışı etkileri ele alınmıştır. Penisilinlerin serviks ve lösemik kanser hücrelerinin çoğalmasını durdurma konusunda ümit vaat edici etkisi ve mantar zehirlenmesi tedavisinde kullanımı; seftriaksonun akciğer kanseri hücreleri üzerindeki çoğalmayı önleyici potansiyeli ve nöroprotektif etkisi derlenmiştir. Tetrasiklinler uzun süredir üzerinde durulan ve araştırılan ajanlardır ve bu gruptaki demeklosiklin, uygunsuz antidiüretik hormon salınımında kullanılmaktadır. Ayrıca tetrasiklinlerden doksisiklin düşük dozda periodontit tedavisi için onay almıştır ve anti-enflamatuvar etkiden sorumlu mekanizma matriks metalloproteinaz (MMP) enzimi inhibisyonudur. Ayrıca MMP inhibisyonu metastazda ve tümör anjiyogenezinde azaltma da sağlayabilmektedir. Diğer bir tetrasiklin olan minosiklin ise Alzheimer ve diğer nörodejeneratif hastalıklarda kilit rolü olan beta-amilod sentezini azaltmakta ve ayrıca gliyal indüklenebilir ...

show abstract

Tetracyclines and Neuromuscular Disorders

Cited by 21 publications

References 46 publications

An Integrative Transcriptome-Wide Analysis of Amyotrophic Lateral Sclerosis for the Identification of Potential Genetic Markers and Drug Candidates

An Integrative Transcriptome-Wide Analysis of Amyotrophic Lateral Sclerosis for the Identification of Potential Genetic Markers and Drug Candidates

The inhibitory effect of minocycline on radiation-induced neuronal apoptosis via AMPKα1 signaling-mediated autophagy

Non Antimicrobial Effects of Antibacterial Agents

Contact Info

Product

Resources

About