Table 2.
Involvement of SLs in neurodegenerative diseases
| Method | Effect | Mechanism | Reference | |
|---|---|---|---|---|
| AD | ||||
| Cortical neurons, Aβ 1–42 | A | ↑exosome release, ↑apoptosis | ↑nSMase, | Wang et al., 2012 |
| Human primary neurons, Aβ | A | ↑ apoptosis | ↑ nSMase | Jana and Pahan, 2004 |
| Cultured hippocampal neurons, Aβ | B | ↑apoptosis | ↑ C18Cer, C24Cer | Cutler et al., 2004 |
| Presenilin knock‐in mouse, primary cultured astrocytes | A | ↑cell death | ↑ C20Cer, C24Cer, ↑CERS1, ↑CERS4 | Wang et al., 2008 |
| Astrocytes, frontal cortex, CSF, patients | B | – | ↑Cer | Satoi et al., 2005 |
| White matter temporal cortex, white and grey matter, patients | B | – | ↑ C24:1Cer, ↓sulfatides | Han et al., 2002 |
| Medial frontal gyrus, patients | B | – | ↑ C24:0 Cer | Cutler et al., 2004 |
| Cultured neurons, Aβ, brain, patients | A, B | ↑Apoptosis | ↑a,nSMase, ↑acid CDase, ↑aSMase, ↑acid CDase, ↑Cer, ↓SM | He et al., 2010 |
| Entorhinal cortex,patients, Hippocampus, temporal grey matter | B | amyloid deposit | ↓SPHK1, ↓S1P1R, ↑SPL, ↓S1P, ↓SPHK1,2, ↑C16:0 Cer | Ceccom et al., 2014 |
| Brodman areas 46,10,20 patients, | B | – | ↑ PPAP2B, ↑ SPL, ↓acid CDase, ↑CERS1,2, ↓CERS6 | Katsel et al., 2007 |
| PD | ||||
| Anterior cingulate cortex, patients | B | – | ↓total Cer, ↓SM, ↑CERS1 expression | Abbott et al., 2014 |
| Anterior cingulate cortex, patients | B | ↑ autophagy ↑α‐synuclein | ↓glucosylCDase, ↓Cer, | Murphy et al., 2014 |
| MS | ||||
| White matter, patients | B | – | ↓S1P, ↑Sph, ↑C16Cer, ↑C18Cer | Qin et al., 2010 |
| Reactive astrocytes, patients | B | – | ↑ C18:0 Cer | Kim et al., 2012 |
| NPC | – | – | – | – |
| NPC−/− mouse brain | B | – | ↑glucosylCer, galactosylCer, glucosylSph, GM2, GM3 | Marques et al., 2015 |
| NPC−/− mouse brain with GBA2 deletion, | B | improved motor coordination | ↑glucosylCer, glucosylSph, =cholesterol, =gangliosides | Marques et al., 2015 |
| NPC1−/− mouse brain, miglustat Patients, plasma Patients + miglustat, plasma patients + miglustat, CSF | B | – | GCS inhibition, ↑ monohexylCer, ↑ monohexylCer, ↑C16:0Cer, ↓Sph, ↑S1P, ↓Cer, ↓GM1, ↓GM3, ↑monohexylCer | Fan et al., 2013 |
| NPC1−/− mouse brain, miglustat, | B | ↑synaptic plasticity | GCS inhibition | D'Arcangelo et al., 2016 |
| Purkinje neurons from NPC1−/− cat, miglustat | A/B | ↑survival | GCS inhibition | Stein et al., 2012 |
| NPC1−/− cat, miglustat | B | ↑lifespan, ↓ motor deficit | GCS inhibition | Stein et al., 2012 |
| Lymphocytes NPC patients, miglustat | A | correction of abnormal lipid trafficking | GCS inhibition | Lachmann et al., 2004 |
The table illustrates some examples of the involvement of SLs in neuroinflammation, ischaemia and in neurogenerative diseases such as PD, MS, AD and NPC, indicating the experimental method used (A: in vitro; B, in vivo; si: siRNA; Cer, ceramide; GBA2, non‐lysosomal glucosylCDase). The alterations in SL concentration or in expression/activity of enzymes involved in SL metabolism are listed under Mechanism.