scholarly journals Deficient neurotransmitter systems and synaptic function in frontotemporal lobar degeneration—Insights into disease mechanisms and current therapeutic approaches

2021 ◽  
Author(s):  
Nadine Huber ◽  
Sonja Korhonen ◽  
Dorit Hoffmann ◽  
Stina Leskelä ◽  
Hannah Rostalski ◽  
...  
Keyword(s):  
Frontotemporal Lobar Degeneration ◽  
Eating Habits ◽  
Neuropsychiatric Symptoms ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Symptomatic Treatment ◽  
Current Treatment ◽  
Synaptic Function ◽  
Model Systems ◽  
Neurotransmitter Systems

AbstractFrontotemporal lobar degeneration (FTLD) comprises a heterogenous group of fatal neurodegenerative diseases and, to date, no validated diagnostic or prognostic biomarkers or effective disease-modifying therapies exist for the different clinical or genetic subtypes of FTLD. Current treatment strategies rely on the off-label use of medications for symptomatic treatment. Changes in several neurotransmitter systems including the glutamatergic, GABAergic, dopaminergic, and serotonergic systems have been reported in FTLD spectrum disease patients. Many FTLD-related clinical and neuropsychiatric symptoms such as aggressive and compulsive behaviour, agitation, as well as altered eating habits and hyperorality can be explained by disturbances in these neurotransmitter systems, suggesting that their targeting might possibly offer new therapeutic options for treating patients with FTLD. This review summarizes the present knowledge on neurotransmitter system deficits and synaptic dysfunction in model systems and patients harbouring the most common genetic causes of FTLD, the hexanucleotide repeat expansion in C9orf72 and mutations in the granulin (GRN) and microtubule-associated protein tau (MAPT) genes. We also describe the current pharmacological treatment options for FLTD that target different neurotransmitter systems.

scholarly journals Pharmacological Interventions for Pulmonary Involvement in Rheumatic Diseases

2021 ◽  
Vol 14 (3) ◽  
pp. 251 ◽  
Author(s):  
Eun Ha Kang ◽  
Yeong Wook Song
Keyword(s):  
Rheumatic Diseases ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Pulmonary Involvement ◽  
Current Treatment ◽  
Targeted Agents ◽  
Pharmacological Interventions ◽  
Inflammatory Processes ◽  
Pulmonary Arterial ◽  
Epidemiologic Features

Among the diverse forms of lung involvement, interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are two important conditions in patients with rheumatic diseases that are associated with significant morbidity and mortality. The management of ILD and PAH is challenging because the current treatment often provides only limited patient survival benefits. Such challenges derive from their common pathogenic mechanisms, where not only the inflammatory processes of immune cells but also the fibrotic and proliferative processes of nonimmune cells play critical roles in disease progression, making immunosuppressive therapy less effective. Recently, updated treatment strategies adopting targeted agents have been introduced with promising results in clinical trials for ILD ad PAH. This review discusses the epidemiologic features of ILD and PAH among patients with rheumatic diseases (rheumatoid arthritis, myositis, and systemic sclerosis) and the state-of-the-art treatment options, focusing on targeted agents including biologics, antifibrotic agents, and vasodilatory drugs.

scholarly journals Neuropsychiatric symptoms in Parkinson's disease: aetiology, diagnosis and treatment

2020 ◽  
Vol 26 (6) ◽  
pp. 333-342 ◽  
Author(s):  
Shoned Jones ◽  
Kelli M. Torsney ◽  
Lily Scourfield ◽  
Katie Berryman ◽  
Emily J. Henderson
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuropsychiatric Symptoms ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Motor Disorder ◽  
Dopamine Dysregulation Syndrome ◽  
Disease Aetiology ◽  
Neuropsychiatric Manifestations ◽  
Assessment Scales

SUMMARYHistorically, Parkinson's disease was viewed as a motor disorder and it is only in recent years that the spectrum of non-motor disorders associated with the condition has been fully recognised. There is a broad scope of neuropsychiatric manifestations, including depression, anxiety, apathy, psychosis and cognitive impairment. Patients are more predisposed to delirium, and Parkinson's disease treatments give rise to specific syndromes, including impulse control disorders, dopamine agonist withdrawal syndrome and dopamine dysregulation syndrome. This article gives a broad overview of the spectrum of these conditions, describes the association with severity of Parkinson's disease and the degree to which dopaminergic degeneration and/or treatment influence symptoms. We highlight useful assessment scales that inform diagnosis and current treatment strategies to ameliorate these troublesome symptoms, which frequently negatively affect quality of life.

Selected natural and synthetic agents effective against Parkinson’s disease with diverse mechanisms

2021 ◽  
Vol 21 ◽  
Author(s):  
Hayrettin Ozan Gulcan
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Dopamine Metabolism ◽  
Dopaminergic Agonists ◽  
Alternative Drug ◽  
Synthetic Agents ◽  
Disease Modifying

: Similar to other neurodegenerative diseases, Parkinson’s disease (PD) has been extensively investigated with respect to its neuropathological background and possible treatment options. Since the symptomatic outcomes are generally related to dopamine deficiency, the current treatment strategies towards PD mainly employ dopaminergic agonists as well as the compounds acting on dopamine metabolism. These drugs do not provide disease modifying properties; therefore alternative drug discovery studies focus on targets involved in the progressive neurodegenerative character of PD. This study has aimed to present the pathophysiology of PD concomitant to the representation of drugs and promising molecules displaying activity against the validated and non-validated targets of PD.

scholarly journals What does first-line therapy mean for paediatric multiple sclerosis in the current era?

2020 ◽  
pp. 135245852093764
Author(s):  
Yael Hacohen ◽  
Brenda Banwell ◽  
Olga Ciccarelli
Keyword(s):  
Multiple Sclerosis ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Cognitive Outcome ◽  
First Line ◽  
First Line Therapy ◽  
Highly Active ◽  
Paediatric Multiple Sclerosis ◽  
The Impact

Paediatric multiple sclerosis (MS) is associated with higher relapse rate, rapid magnetic resonance imaging lesion accrual early in the disease course and worse cognitive outcome and physical disability in the long term compared to adult-onset disease. Current treatment strategies are largely centre-specific and reliant on adult protocols. The aim of this review is to examine which treatment options should be considered first line for paediatric MS and we attempt to answer the question if injectable first-line disease-modifying therapies (DMTs) are still an optimal option. To answer this question, we review the effects of early onset disease on clinical course and outcomes, with specific considerations on risks and benefits of treatments for paediatric MS. Considering the impact of disease activity on brain atrophy, cognitive impairment and development of secondary progressive MS at a younger age, we would recommend treating paediatric MS as a highly active disease, favouring the early use of highly effective DMTs rather than injectable DMTs.

scholarly journals Role of the Myokine Irisin on Bone Homeostasis: Review of the Current Evidence

2021 ◽  
Vol 22 (17) ◽  
pp. 9136
Author(s):  
Amanda Kornel ◽  
Danja J. Den Hartogh ◽  
Panagiota Klentrou ◽  
Evangelia Tsiani
Keyword(s):  
Bone Resorption ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Current Evidence ◽  
Signaling Proteins ◽  
Bone Homeostasis ◽  
Menopausal Women ◽  
Post Menopausal

Bone is a highly dynamic tissue that is constantly adapting to micro-changes to facilitate movement. When the balance between bone building and resorption shifts more towards bone resorption, the result is reduced bone density and mineralization, as seen in osteoporosis or osteopenia. Current treatment strategies aimed to improve bone homeostasis and turnover are lacking in efficacy, resulting in the search for new preventative and nutraceutical treatment options. The myokine irisin, since its discovery in 2012, has been shown to play an important role in many tissues including muscle, adipose, and bone. Evidence indicate that irisin is associated with increased bone formation and decreased bone resorption, leading to reduced risk of osteoporosis in post-menopausal women. In addition, low serum irisin levels have been found in individuals with osteoporosis and osteopenia. Irisin targets key signaling proteins, promoting osteoblastogenesis and reducing osteoclastogenesis. The present review summarizes the existing evidence regarding the effects of irisin on bone homeostasis.

scholarly journals Animal models of regenerative medicine for biological treatment approaches of degenerative disc diseases

2020 ◽  
pp. 153537022096912
Author(s):  
Demissew Shenegelegn Mern ◽  
Tanja Walsen ◽  
Anja Beierfuß ◽  
Claudius Thomé
Keyword(s):  
Animal Models ◽  
Biological Treatment ◽  
Chronic Back Pain ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Disc Disease ◽  
Treatment Approaches ◽  
Degenerative Disc ◽  
And Function

Degenerative disc disease (DDD) is a painful, chronic and progressive disease, which is characterized by inflammation, structural and biological deterioration of the intervertebral disc (IVD) tissues. DDD is specified as cell-, age-, and genetic-dependent degenerative process that can be accelerated by environmental factors. It is one of the major causes of chronic back pain and disability affecting millions of people globally. Current treatment options, such as physical rehabilitation, pain management, and surgical intervention, can provide only temporary pain relief. Different animal models have been used to study the process of IVD degeneration and develop therapeutic options that may restore the structure and function of degenerative discs. Several research works have depicted considerable progress in understanding the biological basis of disc degeneration and the therapeutic potentials of cell transplantation, gene therapy, applications of supporting biomaterials and bioactive factors, or a combination thereof. Since animal models play increasingly significant roles in treatment approaches of DDD, we conducted an electronic database search on Medline through June 2020 to identify, compare, and discuss publications regarding biological therapeutic approaches of DDD that based on intradiscal treatment strategies. We provide an up-to-date overview of biological treatment strategies in animal models including mouse, rat, rabbit, porcine, bovine, ovine, caprine, canine, and primate models. Although no animal model could profoundly reproduce the clinical conditions in humans; animal models have played important roles in specifying our knowledge about the pathophysiology of DDD. They are crucial for developing new therapy approaches for clinical applications.

scholarly journals Current Treatment Options for Cystic Fibrosis-Related Liver Disease

2020 ◽  
Vol 21 (22) ◽  
pp. 8586 ◽  
Author(s):  
Katharina Staufer
Keyword(s):  
Cystic Fibrosis ◽  
Liver Disease ◽  
Current Knowledge ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Transmembrane Conductance Regulator ◽  
Definition Of ◽  
Related Liver Disease ◽  
Near Future

Cystic Fibrosis-related liver disease (CFLD) has become a leading cause of morbidity and mortality in patients with Cystic Fibrosis (CF), and affects children and adults. The understanding of the pathogenesis of CFLD is key in order to develop efficacious treatments. However, it remains complex, and has not been clarified to the last. The search for a drug might be additionally complicated due to the diverse clinical picture and lack of a unified definition of CFLD. Although ursodeoxycholic acid has been used for decades, its efficacy in CFLD is controversial, and the potential of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulators and targeted gene therapy in CFLD needs to be defined in the near future. This review focuses on the current knowledge on treatment strategies for CFLD based on pathomechanistic viewpoints.

scholarly journals Management of Chyle Leak after Head and Neck Surgery: Review of Current Treatment Strategies

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Sean W. Delaney ◽  
Haoran Shi ◽  
Alireza Shokrani ◽  
Uttam K. Sinha
Keyword(s):  
Head And Neck ◽  
Thoracic Duct ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Neck Surgery ◽  
Current Treatment ◽  
The Body ◽  
Head And Neck Surgery ◽  
Chyle Leak ◽  
Electrolyte Disturbances

Chyle leak formation is an uncommon but serious sequela of head and neck surgery when the thoracic duct is inadvertently injured, particularly with the resection of malignancy low in the neck. The thoracic duct is the primary structure that returns lymph and chyle from the entire left and right lower half of the body. Chyle extravasation can result in delayed wound healing, dehydration, malnutrition, electrolyte disturbances, and immunosuppression. Prompt identification and treatment of a chyle leak are essential for optimal surgical outcome. In this article we will review the current treatment options for iatrogenic cervical chyle leaks.

scholarly journals Novel 3D µtissues Mimicking the Fibrotic Stroma in Pancreatic Cancer to Study Cellular Interactions and Stroma-Modulating Therapeutics

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 5006
Author(s):  
Kunal P. Pednekar ◽  
Marcel A. Heinrich ◽  
Joop van Baarlen ◽  
Jai Prakash
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Cells ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Collagen Gel ◽  
Current Treatment ◽  
Ductal Adenocarcinoma ◽  
Tumor Type ◽  
Cellular Interactions

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor type with low patient survival due to the low efficacy of current treatment options. Cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) create a dense fibrotic environment around the tumor cells, preventing therapies from reaching their target. Novel 3D in vitro models are needed that mimic this fibrotic barrier for the development of therapies in a biologically relevant environment. Here, novel PDAC microtissues (µtissues) consisting of pancreatic cancer cell core surrounded by a CAF-laden collagen gel are presented, that is based on the cells own contractility to form a hard-to-penetrate barrier. The contraction of CAFs is demonstrated facilitating the embedding of tumor cells in the center of the µtissue as observed in patients. The µtissues displayed a PDAC-relevant gene expression by comparing their gene profile with transcriptomic patient data. Furthermore, the CAF-dependent proliferation of cancer cells is presented, as well as the suitability of the µtissues to serve as a platform for the screening of CAF-modulating therapies in combination with other (nano)therapies. It is envisioned that these PDAC µtissues can serve as a high-throughput platform for studying cellular interactions in PDAC and for evaluating different treatment strategies in the future.

scholarly journals Management of Acute Myeloid Leukemia: Current Treatment Options and Future Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5722
Author(s):  
Maximilian Fleischmann ◽  
Ulf Schnetzke ◽  
Andreas Hochhaus ◽  
Sebastian Scholl
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Current Status ◽  
Epigenetic Therapy ◽  
Comprehensive Overview ◽  
Secondary Resistance ◽  
Acute Myeloid

Treatment of acute myeloid leukemia (AML) has improved in recent years and several new therapeutic options have been approved. Most of them include mutation-specific approaches (e.g., gilteritinib for AML patients with activating FLT3 mutations), or are restricted to such defined AML subgroups, such as AML-MRC (AML with myeloid-related changes) or therapy-related AML (CPX-351). With this review, we aim to present a comprehensive overview of current AML therapy according to the evolved spectrum of recently approved treatment strategies. We address several aspects of combined epigenetic therapy with the BCL-2 inhibitor venetoclax and provide insight into mechanisms of resistance towards venetoclax-based regimens, and how primary or secondary resistance might be circumvented. Furthermore, a detailed overview on the current status of AML immunotherapy, describing promising concepts, is provided. This review focuses on clinically important aspects of current and future concepts of AML treatment, but will also present the molecular background of distinct targeted therapies, to understand the development and challenges of clinical trials ongoing in AML patients.

Sign in / Sign up

Export Citation Format

Share Document