The Niemann-Pick type diseases – A synopsis of inborn errors in sphingolipid and cholesterol metabolism

Optical recordings of organellar membrane potentials and the components of membrane conductance in lysosomes

“…Currently, there is great interest in studying the ion fluxes across the lysosomal membrane, which are regulated by a distinct set of channels and transporters (Chen et al, 2017;Li et al, 2019;Sterea et al, 2018;. These have been implicated in various human pathological conditions associated with lysosomal storage diseases, such as neurodegenerative diseases, metabolic disorders and cancer (Ellison et al, 2023;Pfrieger, 2023;Shin et al, 2019;Toledano-Zaragoza & Ledesma, 2020). Lysosomal storage diseases can arise from mutations in lysosomal enzymes, but naturally occurring variations in the expression and/or function of lysosomal ion channels and transporters can also lead to lysosomal storage diseases (Bissa et al, 2016;Cao et al, 2015;Feng et al, 2018;Huizing & Gahl, 2020;Kendall & Holian, 2021;Onyenwoke et al, 2015;Riederer et al, 2023;Shen et al, 2012;Zhang et al, 2018).…”

Pulmonary Surfactant: A Mighty Thin Film

“…117−120 These latter two conditions, however, are multisystemic, in which many additional organs are affected. 121,122 In summary, although this review is mainly dedicated toward understanding the biophysical properties of pulmonary surfactant, and these obviously impact RDS and ARDS, it has become clear that surfactant has other important functions in health and disease. The impact of surfactant, and its individual components, on the lung may either directly or indirectly be associated with its activity at the alveolar interface.…”

“…Mutations in SP-A, SP-B, and SP-C have all been reported in the human population. , Many of the clinical observations are phenocopied in animals, showing, for example, that SP-B expression is essential for surfactant function and hence life ,, and that SP-C mutations, although not lethal, are often associated with the development of childhood or adult pulmonary fibrosis. , Other mutations, for example in the gene encoding for thyroid transcription factor-1 (TTF-1), a transcription factor for surfactant proteins, and the ABCA3 transporter, responsible for intracellular transport of surfactant lipids, can impact the surfactant system as well . Mutations in ABCA3 can affect intracellular lamellar body size and content, resulting in Type II cell dysplasia which contributes to pulmonary fibrosis. , Other mutations, such as those associated with Niemann–Pick Disease and Hermansky–Pudlak Syndrome, also affect surfactant metabolism and lung function. − These latter two conditions, however, are multisystemic, in which many additional organs are affected. , …”

Nanoreporter Identifies Lysosomal Storage Disease Lipid Accumulation Intracranially

“…5 Indeed, studies performed on a knockout mouse model lacking ASM and with cells derived from patients show that intralysosomal accumulation of SM is a primary pathological event. 6 In the brain, the defective homeostasis of SM leads to neurodegeneration that initially affects Purkinje neurons in the cerebellum 7−9 and further involves astrogliosis, high oxidative stress, increased intracellular calcium, 10 and autophagy. 11 Neurons deficient in ASM are also characterized by increased SM in the plasma membrane, unpolarized distribution of proteins, dendritic spine anomalies, 12 and impaired synaptic vesicle docking.…”

“…In NPA, loss-of-function mutations in the SMPD1 gene encoding ASM lead to the accumulation of SM within lysosomes in cells and tissues . Indeed, studies performed on a knockout mouse model lacking ASM and with cells derived from patients show that intralysosomal accumulation of SM is a primary pathological event . In the brain, the defective homeostasis of SM leads to neurodegeneration that initially affects Purkinje neurons in the cerebellum − and further involves astrogliosis, high oxidative stress, increased intracellular calcium, and autophagy .…”