Unique recombinant progranulin protein that binds to sortilin

Progranulin (PGRN) is a cysteine-rich protein, composed of seven ~6kDa granulin (GRN) proteins, that shows multifunctional biological activities, including major roles in cancer, inflammation, metabolic disease and neurodegeneration, especially as a valuable biomarker for Frontotemporal Lobar Degeneration (FTLD). PGRN is an abundant, non-conventional, stress-induced, extracellular matrix-bound secreted growth factor-like molecule and cytoplasmic chaperone, that functions in a cellular and disease specific pattern. PGRN binds to several functionally different receptor families in a cell/tissue specific and condition/disease-dependent manner. For example, PGRN binding with TNFR and DR3 has an important anti-inflammatory role in immune cells, particularly Tregs and macrophages. PGRN/Ephrin type-A receptor 2 (EphA2) interaction is involved in the proliferative influence of PGRN. PGRN binds and activates Notch receptors, enhancing the regenerative capacity of injured neurons. PGRN is also a lysosomal resident protein and sortilin and lipoprotein receptor-related protein 1 (LRP1) have been demonstrated to be the lysosomal trafficking receptors for PGRN with the help of Prosaposin. In the brain, PGRN is primarily expressed in mature neurons and microglia. Absence of progranulin in microglia causes increased production and release of multiple cytokines, suggesting that PGRN regulates microglia activation. PGRN seems to affect microglial proliferation, recruitment, differentiation, activation and phagocytosis, suggesting that PGRN plays a central role in the regulation of neuroinflammatory responses. In neurons, PGRN i) co-localizes in late endosomes and early lysosomes with the transmembrane protein TMEM106B, ii) co-localizes with markers such as BDNF along axons, iii) influences synaptic structure and function at synaptic and extra-synaptic sites, where it is secreted in an activity-dependent manner, and iv) extracellular PGRN is endocytosed and delivered to lysosomes. The lysosomal function of PGRN is not well characterized, but probably involves regulation of proteins such as cathepsins, glucocerebrosidase (GBA) or TMEM106B and likely contributes to neurodegeneration.

Progranulin expression in plasma predicts GRN mutations status, independently of symptom onset proximity. Progranulin loss-of-function mutations are among the most frequent genetic causes, responsible for 20% of familial FTLD. If a patient carries a mutation in the progranulin gene, it can be detected using AdipoGen’s Progranulin (human) ELISA Kit. This is the only and unique kit on the market detecting all mutations of Progranulin [ref. 4]. See below an overview of AdipoGen Life Sciences’ unique ELISA kits, proteins and antibodies.

Progranulin [PGRN] ELISA kits

Progranulin recombinant proteins

Progranulin antibodies, tagged proteins and related products

References

1. Kao AW, McKay A, Singh PP, Brunet A, Huang EJ. Progranulin, lysosomal regulation and neurodegenerative disease. Nat Rev Neurosci. 2017;18(6):325-333.
2. Paushter DH, Du H, Feng T, Hu F. The lysosomal function of progranulin, a guardian against neurodegeneration. Acta Neuropathol. 2018;136(1):1-17.
3. Cui Y, Hettinghouse A, Liu CJ. Progranulin: A conductor of receptors orchestra, a chaperone of lysosomal enzymes and a therapeutic target for multiple diseases. Cytokine Growth Factor Rev. 2019;45:53-64.
4. Sellami L, Rucheton B, Ben Younes I, et al. Plasma progranulin levels for frontotemporal dementia in clinical practice: a 10-year French experience. Neurobiol Aging. 2020;91:167.e1-167.e9.