Parkinson's disease is the most common neurodegenerative movement disorder. It arises as a result of neuronal cell death in specific brain regions, notably the substantia nigra pars compacta, and is characterized by the accumulation of α-synuclein in these brain regions. Current pharmacological therapies alleviate the motor symptoms of the disease and are particularly effective in the early stages of the disease. Ongoing drug development efforts focus on disease-modifying strategies that aim to halt or slow disease progression. In this review, we explore a number of emerging disease-modifying strategies with a focus on direct and indirect targeting of α-synuclein dysfunction. We summarize newer classes of small molecules and biological agents intended to attenuate protein aggregation or to target enzymes that may increase the degradation of the pathogenic forms of α-synuclein. Finally, we discuss emerging strategies that are demonstrating the potential for disease modification at the preclinical stage.
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http://dx.doi.org/10.1111/bph.14345 | DOI Listing |
J Clin Med
January 2025
Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan.
Rheumatoid arthritis (RA) is an immune-mediated disease characterized by polyarthritis that affects the small joints of the bilateral upper and lower extremities. RA shares several common clinical symptoms with Sjögren's syndrome (SS), another rheumatic disease caused by the lymphocytic infiltration of exocrine glands, with dry eye and dry mouth being the two most common symptoms. Anti-Ro/SS-A antibodies, a diagnostic biomarker of SS, are positive in patients with RA at a certain rate.
View Article and Find Full Text PDFChildren (Basel)
January 2025
Department of Children's Diseases, N.F. Filatov Clinical Institute of Children's Health, I.M. Sechenov First Moscow State Medical University, 119435 Moscow, Russia.
Takayasu's arteritis (TA) is a systemic vasculitis that primarily affects the aorta and major arteries. Despite aggressive treatment with glucocorticoids (GCs) and non-biological disease-modifying antirheumatic drugs (nbDMARDs), about 30% of patients experience resistance to therapy or relapse. This study aimed to identify risk factors associated with refractory and relapse TA in pediatric patients.
View Article and Find Full Text PDFDiabetes Res Clin Pract
January 2025
Department of Medicine, Division of Endocrinology, Diabetes and Clinical Nutrition, Oregon Health & Science University, Portland USA.
Background: Diabetic neuropathy (DN) affects up to half of individuals with type 1 and type 2 diabetes. Despite evidence that improving metabolic and cardiovascular health can slow its progression, DN remains a significant clinical challenge due to the lack of disease-modifying therapies and effective pain management strategies. This consensus aimed to identify gaps and recommend strategies to address these challenges.
View Article and Find Full Text PDFClin Epigenetics
January 2025
School of Forensic Medicine, China Medical University, Shenyang, People's Republic of China.
Enriched environment (EE), as a non-pharmacological intervention, has garnered considerable attention for its potential to ameliorate neurodegenerative diseases (NDs). This review delineated the impact of EE on the biological functions associated with NDs, emphasizing its role in enhancing neural plasticity, reducing inflammation, and bolstering cognitive performance. We discussed the molecular underpinnings of the effects of EE, including modulation of key signaling pathways such as extracellular regulated kinase 1/2 (ERK1/2), mitogen-activated protein kinases (MAPK), and AMPK/SIRT1, which were implicated in neuroprotection and synaptic plasticity.
View Article and Find Full Text PDFAutoimmun Rev
January 2025
Department of Neurology, Hannover Medical School, 30625 Hannover, Germany. Electronic address:
A wide variety of immunomodulatory therapies are already available for the treatment of multiple sclerosis (MS). Through fundamental insights from basic research with a gain of knowledge in the pathological processes underlying MS, the exploration of additional medical compounds within clinical trials has been ignited. Emerging novel medications with innovative mechanisms of action are being introduced.
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