The lysosomal storage disease continuum with ageing-related neurodegenerative disease

Lloyd-Evans, Emyr; Haslett, Luke J.

doi:10.1016/j.arr.2016.07.005

Cited by 42 publications

(40 citation statements)

References 236 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…With exciting new genetic and clinical links between LSD and adult‐onset neurodegenerative diseases such as sporadic Parkinson's disease, it is imperative to systematically define the spectrum of movement disorders in childhood‐onset LSD. Here we systematically investigated the presence of movement disorders in a large cohort of children with genetically or biochemically confirmed LSD.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The Spectrum of Movement Disorders in Childhood‐onset Lysosomal Storage Diseases

Ebrahimi‐Fakhari

Hildebrandt

Davis

et al. 2018

Movement Disord Clin Pract

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

“…With exciting new genetic and clinical links between LSD and adult-onset neurodegenerative diseases such as sporadic Parkinson's disease, 10,11 it is imperative to systematically define the spectrum of movement disorders in childhood-onset LSD.…”

Section: Discussionmentioning

confidence: 99%

The Spectrum of Movement Disorders in Childhood‐onset Lysosomal Storage Diseases

Ebrahimi‐Fakhari

Hildebrandt

Davis

et al. 2018

Movement Disord Clin Pract

View full text Add to dashboard Cite

show abstract

“…Lysosomal storage disorders and neurodegenerative diseases (Alzheimer’s, Parkinson’s and Huntington diseases) share many features related to the mechanisms that characterize the disease pathogenesis [63]. The first link between LSDs and Parkinson’s disease (PD) have been demonstrated a decade ago for Gaucher disease, and then extended to others, such as Niemann–Pick type I e II (NPC1, NPC2), GM1 and GM2 gangliosidosis, neuronal ceroid lipofuscinoses and Fabry disease [64].…”

Section: Discussionmentioning

confidence: 99%

“…The up-regulation of α-synuclein ( Snca ), identified in both areas of the Ids-ko mouse, is very important as its peptides are a major component of amyloid plaques in the brains of patients with AD, while defects in Snca have been involved in the death of dopaminergic neurons in the pathogenesis of PD [63]. In the Ids-ko brains, we found differentially expressed genes involved in different stages of PD pathway, from proteasome dysfunction to mitochondrial impairment and oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Brain RNA-Seq Profiling of the Mucopolysaccharidosis Type II Mouse Model

Salvalaio

D’Avanzo

Rigon

et al. 2017

IJMS

View full text Add to dashboard Cite

Lysosomal storage disorders (LSDs) are a group of about 50 genetic metabolic disorders, mainly affecting children, sharing the inability to degrade specific endolysosomal substrates. This results in failure of cellular functions in many organs, including brain that in most patients may go through progressive neurodegeneration. In this study, we analyzed the brain of the mouse model for Hunter syndrome, a LSD mostly presenting with neurological involvement. Whole transcriptome analysis of the cerebral cortex and midbrain/diencephalon/hippocampus areas was performed through RNA-seq. Genes known to be involved in several neurological functions showed a significant differential expression in the animal model for the disease compared to wild type. Among the pathways altered in both areas, axon guidance, calcium homeostasis, synapse and neuroactive ligand–receptor interaction, circadian rhythm, neuroinflammation and Wnt signaling were the most significant. Application of RNA sequencing to dissect pathogenic alterations of complex syndromes allows to photograph perturbations, both determining and determined by these disorders, which could simultaneously occur in several metabolic and biochemical pathways. Results also emphasize the common, altered pathways between neurodegenerative disorders affecting elderly and those associated with pediatric diseases of genetic origin, perhaps pointing out a general common course for neurodegeneration, independent from the primary triggering cause.

show abstract

“…Currently, the hypothesis is beginning to emerge which suggests that neurodegenerative disorders share similarities in terms of underlying pathogenic mechanisms with lysosomal storage diseases (LSDs) [6]. Thus, dysfunctional mitochondria, impaired autophagy and accumulation of cytoplasmic protein aggregates are frequent alterations shared by LSDs and more common neurodegenerative disorders [7,8,9].…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Dysfunction in Lysosomal Storage Disorders

et al. 2016

View full text Add to dashboard Cite

Lysosomal storage diseases (LSDs) describe a heterogeneous group of rare inherited metabolic disorders that result from the absence or loss of function of lysosomal hydrolases or transporters, resulting in the progressive accumulation of undigested material in lysosomes. The accumulation of substances affects the function of lysosomes and other organelles, resulting in secondary alterations such as impairment of autophagy, mitochondrial dysfunction, inflammation and apoptosis. LSDs frequently involve the central nervous system (CNS), where neuronal dysfunction or loss results in progressive neurodegeneration and premature death. Many LSDs exhibit signs of mitochondrial dysfunction, which include mitochondrial morphological changes, decreased mitochondrial membrane potential (ΔΨm), diminished ATP production and increased generation of reactive oxygen species (ROS). Furthermore, reduced autophagic flux may lead to the persistence of dysfunctional mitochondria. Gaucher disease (GD), the LSD with the highest prevalence, is caused by mutations in the GBA1 gene that results in defective and insufficient activity of the enzyme β-glucocerebrosidase (GCase). Decreased catalytic activity and/or instability of GCase leads to accumulation of glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph) in the lysosomes of macrophage cells and visceral organs. Mitochondrial dysfunction has been reported to occur in numerous cellular and mouse models of GD. The aim of this manuscript is to review the current knowledge and implications of mitochondrial dysfunction in LSDs.

show abstract

The lysosomal storage disease continuum with ageing-related neurodegenerative disease

Cited by 42 publications

References 236 publications

The Spectrum of Movement Disorders in Childhood‐onset Lysosomal Storage Diseases

The Spectrum of Movement Disorders in Childhood‐onset Lysosomal Storage Diseases

Brain RNA-Seq Profiling of the Mucopolysaccharidosis Type II Mouse Model

Mitochondrial Dysfunction in Lysosomal Storage Disorders

Contact Info

Product

Resources

About