Protein alteration adds to degeneration of neuronal populaces in Huntington’s infection

Protein alteration adds to degeneration of neuronal populaces in Huntington’s infection


  • Post By : Kumar Jeetendra

  • Source: University of Barcelona

  • Date: 01 Feb,2021

A study in which UB scientists have taken part states that alterations in the levels of one of those proteins, lamin B1, add to the degeneration of distinct brain neuronal populations in Huntington’s disease. Caused by a mutation in the huntingtin gene, this pathology features involuntary movements, cognitive deficit, and psychiatric disorders, and has no cure yet.

According to the study, published in the journalEMBO Molecular Medicine, these results open new therapeutic pathways for treating this disorder, since research shows pharmacological normalization of levels of lamin B1 improves the cognitive symptoms in a transgenic model of the disease.

The study counts on the participation of researchers of the Institute of Neurosciences at the University of Barcelona (UBNeuro), the Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), and the August Pi I Sunyer Biomedical Research Institute (IDIBAPS), and is directed by Esther Pérez-Navarro, tenured university lecturer at the Faculty of Medicine and Health Sciences.

An innovative method to analyze cell nucleus

The level increase of lamin B1, a protein in the cell nucleus, causes a rare disorder, the autosomal dominant leukodystrophy, which includes a motor and cognitive deficits and demyelination in the central nervous system. In this study, researchers analyzed the effect at a physiological, transcriptomic, and epigenetic amount of those alterations in Huntington’s disease.

Among the most relevant aspects of the research is the development of an innovative technique, the fluorescence-activated nuclear suspension imaging (FANSI) to identify and examine the neuron nucleus of specific populations in the mind. “This technique could be used by other research groups”, notes Esther Pérez-Navarro.

Moreover —the researcher adds—, we have applied the ChIP-sequencing technique in collaboration with other research groups experts in this technique and the interpretation of results: the groups led by Mashami Narita, from the University of Cambridge, and Luciano Di Croce, from CRG. This allowed us to analyze how the alteration of levels in lamin B1 can involve changes in gene transcription”.

Esther Pérez-Navarro, Tenured University Lecturer, Faculty of Medicine and Health Sciences, Universidad de Barcelona

Later, researchers gave the mice betulinic acid, a drug that could partially restore the amount of lamin B1, to test the effect in the mice models of the disease. Normalization of levels of this protein in the nucleus of neuronal populations palliated motor and cognitive dysfunctions in animals.

According to the researchers, these results show that the level increase of lamin B1 contributes to the alteration of the nuclear function of specific neurons in the brain in Huntington’s disease.

Pérez-Navarro states that”to date, we did not know about the change of the protein being involved in Huntington’s physiopathology”, and she questions whether this alteration could be involved in the neuronal degeneration of other diseases, such as Alzheimer’s and Parkinson’s.

The first step to design new drugs

“Betulinic acid used in this research has other results and therefore we will need to identify specific drugs that target the modulation of lamin B1 levels”, notes the researcher.

Moreover, this study could have implications in the identification of new biomarkers of the disease. In this sense, the future objective of the researchers is to ascertain whether lamin B levels are also altered in cells outside the brain, such as blood cells and fibroblasts (skin cells).

“The advantages of this research in a disease such as Huntington’s, associated with a genetic mutation, is that we can examine these changes in carriers that have no symptoms yet and track it over time. To carry out these studies, we’re working with the Department of Movement Disorders (Jesús Pérez and Jaime Kulisevsky) in Hospital de la Santa Creu I Sant Pau, a distinguished center regarding this disease”, concludes the researcher.

Journal reference:

Alcalá‐Vida, R., et al. (2020) Neuron type‐specific increase in lamin B1 contributes to nuclear dysfunction in Huntington’s disease. EMBO Molecular

About Author