Lysosomal Dysfunction at the Centre of Parkinson's Disease and Frontotemporal Dementia/Amyotrophic Lateral Sclerosis.

Trends Neurosci

Oxford Parkinson's Disease Centre, Department of Physiology Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, OX1 3QX, UK. Electronic address:

Published: December 2019

Parkinson's disease (PD) and frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS) are insidious and incurable neurodegenerative diseases that represent a significant burden to affected individuals, caregivers, and an ageing population. Both PD and FTD/ALS are defined at post mortem by the presence of protein aggregates and the loss of specific subsets of neurons. We examine here the crucial role of lysosome dysfunction in these diseases and discuss recent evidence for converging mechanisms. This review draws upon multiple lines of evidence from genetic studies, human tissue, induced pluripotent stem cells (iPSCs), and animal models to argue that lysosomal failure is a primary mechanism of disease, rather than merely reflecting association with protein aggregate end-points. This review provides compelling rationale for targeting lysosomes in future therapeutics for both PD and FTD/ALS.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6931156PMC
http://dx.doi.org/10.1016/j.tins.2019.10.002DOI Listing

Publication Analysis

Top Keywords

parkinson's disease
8
disease frontotemporal
8
frontotemporal dementia/amyotrophic
8
dementia/amyotrophic lateral
8
lateral sclerosis
8
lysosomal dysfunction
4
dysfunction centre
4
centre parkinson's
4
sclerosis parkinson's
4
sclerosis ftd/als
4

Similar Publications

Study Objectives: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) may improve sleep dysfunction, a common non-motor symptom of Parkinson disease (PD). Improvement in motor symptoms correlates with DBS-suppressed local field potential (LFP) activity, particularly in the beta frequency (13 - 30 Hz). Although well-characterized in the short term, little is known about the innate progression of these oscillations across the sleep-wake cycle.

View Article and Find Full Text PDF

Background: Friedreich ataxia is a rare neurodegenerative disorder caused by frataxin deficiency. Both underweight and overweight occur in mitochondrial disorders, each with adverse health outcomes. We investigated the longitudinal evolution of anthropometric abnormalities in Friedreich ataxia and the hypothesis that both weight loss and weight gain are associated with faster disease progression.

View Article and Find Full Text PDF

: Sexual dysfunction (SD) in Parkinson's Disease (PD) patients is a common and distressing concern, although it remains an underdiagnosed and undertreated condition. Indeed, the prevalence of SD in PD ranges from 42.6% to 79% in men and from 36% to 87.

View Article and Find Full Text PDF

In the medical field, there are several very different movement disorders, such as tremors, Parkinson's disease, or Huntington's disease. A wide range of motor and non-motor symptoms characterizes them. It is evident that in the modern era, the use of smart wrist devices, such as smartwatches, wristbands, and smart bracelets is spreading among all categories of people.

View Article and Find Full Text PDF

In the context of neurodegenerative diseases, finger tapping is a gold-standard test used by clinicians to evaluate the severity of the condition. The finger tapping test involves repetitive tapping between the index finger and thumb. Subjects affected by neurodegenerative diseases, such as Parkinson's disease, often exhibit symptoms like bradykinesia, rigidity, and tremor.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!