Saposin C: neuronal effect and CNS delivery by liposomes

Area of Science:

• Neuroscience
• Cell Biology
• Lysosomal Storage Diseases

Background:

• Prosaposin (PSAP) is a precursor protein for saposin C, a lipid-binding protein with neurotrophic functions.
• Defects in the PSAP gene cause lysosomal storage diseases characterized by multivesicular body (MVB) accumulation and neuronal degeneration.
• Saposin C contains a minimal domain essential for prosaposin's neurotrophic activity.

Purpose of the Study:

• To investigate the role of saposin C in lysosomal storage diseases and neuronal health.
• To evaluate the therapeutic potential of saposin C delivery for correcting MVB accumulation and enhancing neuronal survival.
• To assess the efficacy of liposome-mediated saposin C delivery across the blood-brain barrier.

Main Methods:

• Cultured skin fibroblasts and neurons from PSAP-deficient patients and mice were used.
• Exogenous saposin C-containing liposomes were introduced into cells and animal models.
• Localization studies tracked internalized saposin C within cellular compartments.
• In vivo delivery of saposin C liposomes across the blood-brain barrier was performed in mice.

Main Results:

• PSAP deficiency led to massive MVB accumulation in fibroblasts and CNS neurons, causing neuronal degeneration and reduced lifespan in mice.
• Exogenous saposin C liposomes effectively reduced MVB levels in cultured cells.
• Internalized saposin C localized to late endosomes and lysosomes.
• Liposomal saposin C successfully crossed the blood-brain barrier and reached neuronal cells in vivo.

Conclusions:

• Saposin C plays a vital role in maintaining cellular homeostasis, particularly in neuronal development and growth.
• Liposome-based delivery of saposin C shows promise as a therapeutic strategy for lysosomal storage diseases affecting the nervous system.
• This approach offers a potential avenue for neuron protection, preservation, and regeneration in neurological disorders.