Parkinson disease (PD) is the fastest growing neurological disorder globally and poses substantial management challenges owing to progressive disability, emergence of levodopa-resistant symptoms, and treatment-related complications. In this Review, we examine the current state of research into PD therapies and outline future priorities for advancing our understanding and treatment of the disease. We identify two main research priorities for the coming years: first, slowing the progression of the disease through the integration of sensitive biomarkers and targeted biological therapies, and second, enhancing existing symptomatic treatments, encompassing surgical and infusion therapies, with the goal of postponing complications and improving long-term patient management. The path towards disease modification is impeded by the multifaceted pathophysiology and diverse mechanisms underlying PD. Ongoing studies are directed at α-synuclein aggregation, complemented by efforts to address specific pathways associated with the less common genetic forms of the disease. The success of these efforts relies on establishing robust end points, incorporating technology, and identifying reliable biomarkers for early diagnosis and continuous monitoring of disease progression. In the context of symptomatic treatment, the focus should shift towards refining existing approaches and fostering the development of novel therapeutic strategies that target levodopa-resistant symptoms and clinical manifestations that substantially impair quality of life.
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http://dx.doi.org/10.1038/s41582-024-01034-x | DOI Listing |
BMC Geriatr
January 2025
Department of Neurology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Objectives: Freezing of Gait (FOG) is one of the disabling symptoms in patients with Parkinson's Disease (PD). While it is difficult to early detect because of the sporadic occurrence of initial freezing events. Whether the characteristic of gait impairments in PD patients with FOG during the 'interictal' period is different from that in non-FOG patients is still unclear.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Neurology, Neurological Institute, Taichung Veterans General Hospital, No. 1650, Taiwan Boulevard, Section 4, Taichung, 40705, Taiwan.
This study investigates whether incorporating olfactory dysfunction into motor subtypes of Parkinson's disease (PD) improves associations with clinical outcomes. PD is commonly divided into motor subtypes, such as postural instability and gait disturbance (PIGD) and tremor-dominant PD (TDPD), but non-motor symptoms like olfactory dysfunction remain underexplored. We assessed 157 participants with PD using the University of Pennsylvania Smell Identification Test (UPSIT), Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (M-UPDRS), Montreal Cognitive Assessment (MoCA), 39-item Parkinson's Disease Questionnaire Summary Index (PDQ-39 SI), and 99mTc-TRODAT-1 imaging.
View Article and Find Full Text PDFEur Psychiatry
January 2025
Mental Health Services Noord-Holland-Noord, Alkmaar, the Netherlands; Dutch Clozapine Collaboration Group, Alkmaar, the Netherlands.
Mov Disord
January 2025
Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Background: Perry syndrome (PS) is a rare and fatal hereditary autosomal dominant neurodegenerative disorder caused by mutations in dynactin (DCTN1). PS brains accumulate inclusions positive for ubiquitin, transactive-response DNA-binding protein of 43 kDa (TDP-43), and to a lesser extent dynactin.
Objectives: Little is known regarding the contributions of TDP-43, an RNA binding protein that represses cryptic exon inclusion, in PS.
Ageing Res Rev
January 2025
Department of Pharmaceutics, NIMS Institute of Pharmacy, NIMS University, Jaipur 303121, Rajasthan, India.
Neurodegenerative diseases (NDs) are debilitating disorders characterized by the progressive and selective loss of function or structure in the brain and spinal cord. Both chronic and acute forms of these diseases are associated with significant morbidity and mortality, as they involve the degeneration of neurons in various brain regions. Misfolding and aggregation of amyloid proteins into oligomer and β-sheet rich fibrils share as common hallmark and lead to neurotoxicity.
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