Complicated spastic paraplegia in patients with
            <i>AP5Z1</i>
            mutations (SPG48)

Hirst, Jennifer; Madeo, Marianna; Smets, Katrien; Edgar, James R.; Schöls, Ludger; Li, Jun; Yarrow, Anna; Deconinck, Tine; Baets, Jonathan; Aken, Elisabeth Van; Bleecker, Jan De; Datiles, Manuel B.; Roda, Ricardo H.; Liepert, Joachim; Züchner, Stephan; Mariotti, Caterina; Jonghe, Peter De; Blackstone, Craig; Kruer, Michael C.

doi:10.1212/nxg.0000000000000098

Cited by 36 publications

(30 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, the levels of bis-monoacylglycerol-phosphate (BMP), which facilitates the degradation of GM2 ganglioside (Anheuser et al, 2015), were reduced in fibroblasts of patients with SERAC1 mutations compared to controls (Wortmann et al, 2012). Importantly, mutations in SPG11, SPG15, SPG48, ATP13A2, and SERAC1 have been associated with parkinsonism in some patients (Ramirez et al, 2006;Anheim et al, 2009;Schicks et al, 2011;Hirst et al, 2016;Ma et al, 2018). The clinical overlap between these patients, as well as the similarities observed in the lysosomal dysfunction suggest that these HSP entities may share some physiopathological pathways, although some differences may exist between them (Vantaggiato et al, 2019).…”

Section: Lysosomal Dysfunctionmentioning

confidence: 99%

Lipids in the Physiopathology of Hereditary Spastic Paraplegias

2020

View full text Add to dashboard Cite

Hereditary spastic paraplegias (HSP) are a group of neurodegenerative diseases sharing spasticity in lower limbs as common symptom. There is a large clinical variability in the presentation of patients, partly underlined by the large genetic heterogeneity, with more than 60 genes responsible for HSP. Despite this large heterogeneity, the proteins with known function are supposed to be involved in a limited number of cellular compartments such as shaping of the endoplasmic reticulum or endolysosomal function. Yet, it is difficult to understand why alteration of such different cellular compartments can lead to degeneration of the axons of cortical motor neurons. A common feature that has emerged over the last decade is the alteration of lipid metabolism in this group of pathologies. This was first revealed by the identification of mutations in genes encoding proteins that have or are supposed to have enzymatic activities on lipid substrates. However, it also appears that mutations in genes affecting endoplasmic reticulum, mitochondria, or endolysosome function can lead to changes in lipid distribution or metabolism. The aim of this review is to discuss the role of lipid metabolism alterations in the physiopathology of HSP, to evaluate how such alterations contribute to neurodegenerative phenotypes, and to understand how this knowledge can help develop therapeutic strategy for HSP.

show abstract

Section: Lysosomal Dysfunctionmentioning

confidence: 99%

Lipids in the Physiopathology of Hereditary Spastic Paraplegias

2020

View full text Add to dashboard Cite

show abstract

“…Thereafter, clinical features included not only prominent spastic paraparesis but also sensory and motor neuropathy, ataxia, dystonia, parkinsonism, and myoclonus. Skin fibroblasts from SPG48 patients tested positive for periodic acid Schiff (PAS) and intrinsic fluorescence material, while electron microscopic analysis indicated lamellar material concordant with abnormal storage of lysosomal material [17].…”

Section: Spg48mentioning

confidence: 99%

Lysosomal Dysfunctions in Hereditary Spastic Paraplegias

Shimazaki¹

2017

Lysosomes - Associated Diseases and Methods to Study Their Function

View full text Add to dashboard Cite

Hereditary spastic paraplegias (HSPs) comprise a heterogeneous group of inherited neurodegenerative diseases with the cardinal feature of a length-dependent degeneration of corticospinal motor axons. They are classified by their mapped genetic loci, SPG1-SPG78. Recently, lysosomal dysfunction is one of the pathomechanism for some autosomalrecessive HSPs. SPG11 is caused by loss-of-function mutations in the SPG11 gene. Its gene product is called spatacsin, which is needed for the recycling of lysosomes from autolysosomes. SPG15 is caused by loss-of-function mutation in the ZFYVE26 gene. The ZFYVE26 gene encodes spastizin. Mutations in spastizin impair autophagosome maturation and lead to an accumulation of immature autophagosomes. SPG48/KIAA0415 encodes AP5Z1, known to be a spatacsin and spastizin interactor. Its mutations lead to loss of protein or mutated forms of protein with defective autophagy. The TECPR2 is a human ATG8-binding protein and positive regulator of autophagy, which plays a key role in major adult and pediatric neurodegenerative diseases. Mutations in the lysosomal trafficking regulator (LYST) gene have been reported to cause hereditary spastic paraplegia. The LYST protein is involved in control of the exocytosis of secretory lysosomes. Recently, Drosophila with a gene mutation of an LYST homolog was revealed to exhibit impaired autophagy.

show abstract

“…In the article "Complicated spastic paraplegia in patients with AP5Z1 mutations (SPG48)" by J. Hirst et al, 1 there is an error in the second sentence of the introduction. The third subunit should read only "z" (zeta) rather than "zz5" as originally published.…”

Section: Complicated Spastic Paraplegia In Patients With Ap5z1 Mutatimentioning

confidence: 99%

Complicated spastic paraplegia in patients with AP5Z1 mutations (SPG48)

2016

Neurol Genet

View full text Add to dashboard Cite

show abstract

Complicated spastic paraplegia in patients with AP5Z1 mutations (SPG48)

Cited by 36 publications

References 21 publications

Lipids in the Physiopathology of Hereditary Spastic Paraplegias

Lipids in the Physiopathology of Hereditary Spastic Paraplegias

Lysosomal Dysfunctions in Hereditary Spastic Paraplegias

Complicated spastic paraplegia in patients with AP5Z1 mutations (SPG48)

Contact Info

Product

Resources

About