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Progranulin (PGRN)

            PGRN is a
secreted, 88 kDa precursor glycoprotein expressed in epithelial cells, neurons,
immune cells, and adipocytes, and promotes neuron survival and neurite (axon or
dendritre) outgrowth, tumor cell growth, would healing, vascularization, and
cell migration 1-2. The GRN gene, the gene that encoded
PGRN, translates a protein with 7.5 granulin tandem repeats, which are rich in
cysteines 3. Eventually, either individual 6 kDa granulins are
released or a combination of linked granulin molecules. Studying PGRN can lead
to understand several human diseases.

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PGRN plays a role in both
neurodegenerative diseases and metabolic diseases 4. The focus
here will be on PGRN’s impact on neurodegenerative diseases. Deficiency in PGRN
secretion in the central nervous system has been correlated with Alzheimer’s
disease, Parkinson’s disease, and mainly FTD, which is characterized by the
atrophy of the frontal and temporal lobes 5. In fact, “FTD sit the
most common neurodegenerative disease in individuals under the age of 60 6.
FTD causes a variety of behavioral symptoms, including but not limited to,
social deficits, impaired learning and memory, anxiety alterations, and
depression-like behaviors 4.

Prosaposin (PSAP)


(PSAP) is a multifunctional glycoprotein protein, that is a precursor protein
for four lysosomal proteins, saposin A, saposin B, saposin C, and saposin D
(Figure 2).  Each saposin has a
propeptide sequence preceding it gets cleaved off during post-translational
modification. Saposins are known for facilitating the hydrolysis of sphingolipids
with lysosomal hydrolases, and each saposin has its own specific role in
promoting this hydrolysis 10, 22. Loss of saposin function results
in an assortment of lysosomal storage diseases, such as Krabbe disease and
Gaucher disease 7-8. Similarly, to PGRN, PSAP promotes cell
survival and neurite outgrowth 9-10. PSAP traffics in and out of
cells mainly by binding to a low-density
lipoprotein receptor-related protein 1 (LRP1) 11. Another
receptor that can mediate PSAP trafficking is a mannose-6-phosphate receptor
(M6PR) 11. PSAP plays an important role in PGRN regulation and
PGRN trafficking. 

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