LRRK2 signaling in neurodegeneration: two decades of progress

2021 ◽  
Author(s):  
Lucia Iannotta ◽  
Elisa Greggio
Keyword(s):  
Progressive Supranuclear Palsy ◽  
Gene Cloning ◽  
Therapeutic Approach ◽  
Late Onset ◽  
Inflammatory Diseases ◽  
Rab Gtpases ◽  
Leucine Rich Repeat ◽  
Common Variants ◽  
Promising Therapeutic Approach ◽  
Cytoskeletal Dynamics

Abstract Leucine-rich repeat kinase 2 (LRRK2) is a complex GTPase/kinase orchestrating cytoskeletal dynamics and multiple steps of the endolysosomal pathway through interaction with a host of partners and phosphorylation of a subset of Rab GTPases. Mutations in LRRK2 cause late-onset Parkinson’s disease (PD) and common variants in the locus containing LRRK2 have been associated with sporadic PD, progressive supranuclear palsy as well as a number of inflammatory diseases. This review encompasses the major discoveries in the field of LRRK2 pathobiology, from the initial gene cloning to the latest progress in LRRK2 inhibition as a promising therapeutic approach to fight neurodegeneration.

scholarly journals microRNAs in human brucellosis: A promising therapeutic approach and biomarker for diagnosis and treatment

2021 ◽  
Author(s):  
Sima Kazemi ◽  
Rasoul Mirzaei ◽  
Mohammad Sholeh ◽  
Sajad Karampoor ◽  
Fariba Keramat ◽  
...  
Keyword(s):  
Therapeutic Approach ◽  
Diagnosis And Treatment ◽  
Human Brucellosis ◽  
Promising Therapeutic Approach

scholarly journals Intermittent rolling is a defect of the extravasation cascade caused by Myosin1e-deficiency in neutrophils

2019 ◽  
Vol 116 (52) ◽  
pp. 26752-26758 ◽  
Author(s):  
Eduardo Vadillo ◽  
Sandra Chánez-Paredes ◽  
Hilda Vargas-Robles ◽  
Idaira María Guerrero-Fonseca ◽  
Ramón Castellanos-Martínez ◽  
...  
Keyword(s):  
Vascular Endothelium ◽  
Actin Polymerization ◽  
Inflammatory Diseases ◽  
Chimeric Mice ◽  
Rolling Velocity ◽  
Chronic Inflammatory Diseases ◽  
Neutrophil Extravasation ◽  
Cytoskeletal Dynamics ◽  
Adhesive Interactions ◽  
Deficient Mice

Neutrophil extravasation is a migratory event in response to inflammation that depends on cytoskeletal dynamics regulated by myosins. Myosin-1e (Myo1e) is a long-tailed class-I myosin that has not yet been studied in the context of neutrophil–endothelial interactions and neutrophil extravasation. Intravital microscopy of TNFα-inflamed cremaster muscles in Myo1e-deficient mice revealed that Myo1e is required for efficient neutrophil extravasation. Specifically, Myo1e deficiency caused increased rolling velocity, decreased firm adhesion, aberrant crawling, and strongly reduced transmigration. Interestingly, we observed a striking discontinuous rolling behavior termed “intermittent rolling,” during which Myo1e-deficient neutrophils showed alternating rolling and jumping movements. Surprisingly, chimeric mice revealed that these effects were due to Myo1e deficiency in leukocytes. Vascular permeability was not significantly altered in Myo1e KO mice. Myo1e-deficient neutrophils showed diminished arrest, spreading, uropod formation, and chemotaxis due to defective actin polymerization and integrin activation. In conclusion, Myo1e critically regulates adhesive interactions of neutrophils with the vascular endothelium and neutrophil extravasation. Myo1e may therefore be an interesting target in chronic inflammatory diseases characterized by excessive neutrophil recruitment.

scholarly journals RNA Editing as a Therapeutic Approach for Retinal Gene Therapy Requiring Long Coding Sequences

2020 ◽  
Vol 21 (3) ◽  
pp. 777 ◽  
Author(s):  
Lewis E. Fry ◽  
Caroline F. Peddle ◽  
Alun R. Barnard ◽  
Michelle E. McClements ◽  
Robert E. MacLaren
Keyword(s):  
Gene Therapy ◽  
Rna Editing ◽  
Therapeutic Approach ◽  
Genetic Diseases ◽  
Point Mutations ◽  
Transcript Level ◽  
Gene Replacement ◽  
Promising Therapeutic Approach ◽  
Pairing Site ◽  
Large Genes

RNA editing aims to treat genetic disease through altering gene expression at the transcript level. Pairing site-directed RNA-targeting mechanisms with engineered deaminase enzymes allows for the programmable correction of G>A and T>C mutations in RNA. This offers a promising therapeutic approach for a range of genetic diseases. For inherited retinal degenerations caused by point mutations in large genes not amenable to single-adeno-associated viral (AAV) gene therapy such as USH2A and ABCA4, correcting RNA offers an alternative to gene replacement. Genome editing of RNA rather than DNA may offer an improved safety profile, due to the transient and potentially reversible nature of edits made to RNA. This review considers the current site-directing RNA editing systems, and the potential to translate these to the clinic for the treatment of inherited retinal degeneration.

scholarly journals Cell therapy for lung disease

2017 ◽  
Vol 26 (144) ◽  
pp. 170044 ◽  
Author(s):  
Sabine Geiger ◽  
Daniela Hirsch ◽  
Felix G. Hermann
Keyword(s):  
Clinical Studies ◽  
Therapeutic Approach ◽  
Lung Diseases ◽  
Distress Syndrome ◽  
Treatment Options ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Cell Therapies ◽  
Promising Therapeutic Approach ◽  
Preclinical And Clinical Studies

Besides cancer and cardiovascular diseases, lung disorders are a leading cause of morbidity and death worldwide. For many disease conditions no effective and curative treatment options are available. Cell therapies offer a novel therapeutic approach due to their inherent anti-inflammatory and anti-fibrotic properties. Mesenchymal stem/stromal cells (MSC) are the most studied cell product. Numerous preclinical studies demonstrate an improvement of disease-associated parameters after MSC administration in several lung disorders, including chronic obstructive pulmonary disease, acute respiratory distress syndrome and idiopathic pulmonary fibrosis. Furthermore, results from clinical studies using MSCs for the treatment of various lung diseases indicate that MSC treatment in these patients is safe. In this review we summarise the results of preclinical and clinical studies that indicate that MSCs are a promising therapeutic approach for the treatment of lung diseases. Nevertheless, further investigations are required.

scholarly journals A case of progressive supranuclear palsy with late-onset supplementary motor area seizure

2010 ◽  
Vol 50 (7) ◽  
pp. 485-488
Author(s):  
Kenji Kamogawa ◽  
Shinya Okuda ◽  
Hitomi Tomita ◽  
Kensho Okamoto ◽  
Bungo Okuda
Keyword(s):  
Progressive Supranuclear Palsy ◽  
Supplementary Motor Area ◽  
Late Onset ◽  
Motor Area

The use of nanoparticles as a promising therapeutic approach in cancer immunotherapy

2015 ◽  
pp. 1-11 ◽  
Author(s):  
Maryam Hosseini ◽  
Mostafa Haji-Fatahaliha ◽  
Farhad Jadidi-Niaragh ◽  
Jafar Majidi ◽  
Mehdi Yousefi
Keyword(s):  
Cancer Immunotherapy ◽  
Therapeutic Approach ◽  
Promising Therapeutic Approach

STEM-17. THE GLIOMA STEM CELL PLATELET INTERACTION DRIVES GBM ONCOGENESIS IDENTIFYING A NOVEL THERAPEUTIC APPROACH

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi24-vi24
Author(s):  
Anthony Sloan ◽  
Harry Hoffman ◽  
Peggy Harris ◽  
Christine Lee-Poturalski ◽  
Theresa Elder ◽  
...  
Keyword(s):  
Median Survival ◽  
Therapeutic Approach ◽  
Cancer Metastasis ◽  
Fold Increase ◽  
Cancer Center ◽  
University Hospitals ◽  
Platelet Counts ◽  
Normal Platelet ◽  
Promising Therapeutic Approach ◽  
Transcriptional Pattern

Abstract The effect of platelets on oncogenesis has been studied extensively in cancer metastasis, but not in glioblastoma (GBM), where metastasis is rare. Here we identify the unique crosstalk between glioma stem cells (GSCs) and platelets within GBM solid tumors that enhance disease progression. Targeting GSCs is considered a promising therapeutic approach; however, no clear method has been identified. High platelet counts have been associated with poor clinical outcome in many cancers including ovarian and endometrial cancer. While platelets are known to affect progression of other tumors, mechanisms by which platelets influence GBM oncogenesis are unknown. Immunofluorescence, qPCR, and western blot were used to evaluate the presence of GSCs and platelets and their colocalization in GBM patient tissue at University Hospitals-Seidman Cancer Center. Functional assays followed by RNA sequencing were conducted to determine the functional effect of healthy and GBM platelets on growth of patient derived, autologous GSCs. Our clinical studies suggest elevated platelet counts positively correlate with GSC proliferation and negatively correlate with overall survival in patients with GBM. Patients with high platelet counts ( >350k/µl) had a median survival time of 9 months compared to 16 months median survival for patients with normal platelet count (150-350/µl) (p<0.05). We demonstrate platelet and GSC co-localization in GBM solid tissue and platelet exposure to patient derived GSCs cell lines results in a ≥ 3-fold increase in GSC proliferation compared to GSCs not exposed to platelets (p<0.0005). Similarly we found that platelets increased the self-renewing capacity by enhancing the average sphere size (p < 0.005), and increasing the GSC “Stem-like” transcriptional pattern (P< 0.05). Conversely, pharmacologic inhibition of platelet activation reversed the effect of platelets on GSC proliferation (p ranging from 0.05-0.005). These studies suggests the platelet-GSC interactions appear to stimulate GBM oncogenesis, identifying a potential therapeutic target for the treatment of GBM.

scholarly journals Low-Frequency Intravesical Electrical Stimulation for the Treatment of Acute Urinary Retention: A Promising Therapeutic Approach

2021 ◽  
Vol 8 ◽  
Author(s):  
Tingting Cao ◽  
Bing Xie ◽  
Siyuan Yang ◽  
Jiaqi Wang ◽  
Xiao Yang ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Urinary Retention ◽  
Therapeutic Approach ◽  
Acute Urinary Retention ◽  
Low Frequency ◽  
Female Rats ◽  
Control Group ◽  
Detrusor Muscle ◽  
Submucosal Layer ◽  
Promising Therapeutic Approach

Acute urinary retention (AUR) is a troublesome urological disease, which causes various lower urinary tract symptoms. However, only few studies explored and evaluated the effective treatments to improve AUR. We aimed to find an effective approach to cure AUR through comparing the efficacy of existing classical low-frequency transcutaneous electrical nerve stimulation (TENS) and novel intravesical electrical stimulation (IVES). A total of 24 AUR female rats were divided into 3 groups as follows: control, TENS, and IVES groups. Rats in the control group had no fake stimulation. Rats in the TENS and IVES groups underwent transcutaneous or intravesical stimulation of a symmetrical biphasic rectangular current pulse with a frequency of 35 Hz, 30 min per day, for seven consecutive days. IVES significantly reduced the actin expression in the submucosal layer but increased its expression in the detrusor layer (p= 0.035,p= 0.001). The neovascularization in the submucosal layer in the IVES group was significantly increased than in the other 2 groups (p= 0.006). Low-frequency IVES performed better than TENS in terms of simultaneously relieving bladder hyperactivity, accelerating epithelial recovery, and strengthening detrusor muscle. IVES may be a promising therapeutic approach for bladder dysfunction, specifically for AUR and overactive bladder in clinical practice.

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