Monday, 01 April 2019 11:46

Hannover: Investigation of a Rare Genetic Disease with Cell Cultures Featured

Using cell cultures, a German-Lebanese research team has done research into biochemical fundamental of the hereditary Niemann-Pick type C disease. They were able to clarify the relationship between different gene mutations and the function of a cholesterol transporter.


Niemann-Pick type C disease is caused by a change in the NPC1 or NPC2 gene. Symptoms are, for instance, gradually dementia, physical disabilities caused by muscle weakness, seizures, etc. Depending on the type of the mutation, the disease may already outbrake after birth, in childhood or adulthood. NPC1 and NPC2 encode for a protein that transports cholesterol. Scientists assumed so far, that a defect in the protein leads to the accumulation of fats such as cholesterol in the lysosomes of liver, kidney and brain cells. Since these fats would no longer be transported away, cholesterol would not be available as building material for the cell membrane, resulting in a cell damage.

What it takes exactly to develop the different manifestations of the disease was not known so far and has now been examined more closely.  The scientists led by Professor Dr. Hassan Y. Naim from the Institute of Physiological Chemistry of the University of Veterinary Medicine Hannover (TiHo) and colleagues from the medical Hannover University of Applied Sciences (MHH) as well as the Lebanese American University in Beirut have investigated a total of 18 from 400 already described mutations of the MPC1 protein in cell culture.

They observed that in some mutations, the NPC1 protein does not appear in the lysosomes but remains in the endoplamsatic reticulum, where it is decomposed in a shorter time (type 1). Other mutations make that NPC1 reaches the lysosomes, but will not be transported further, followed by a degradation after some time (type 2). In the third type, NPC1 is transported further, but its function could be hindered maybe because of an impaired abillity to bind cholesterol. In these cases, the disease comes only in the adult age to an outbrake with comparatively mild symptoms.

The findings serve as an important basis for further examinations with the patient's own cell material.

The researchers have presented their species in scientific reports:
Shammas, H., Kuech, E.-M., Rizk, S., Das, A. M. & Naim, H. Y. (2019). Different Niemann-Pick C1 Genotypes Generate Protein Phenotypes that Vary in their Intracellular Processing, Trafficking and Localization. Scientific Reports 9/5292. doi: 10,1038/s41598-019-41707-y

Source:
https://idw-online.de/de/news713110

About Niemann-Pick type C disease:
http://www.neurologische-krankheiten.info/neurologische-krankheiten/niemann-pick-typ-c-