The onset mechanisms of the disease have been further clarified; the role of elevated cholesterol levels and the sharing of genes responsible for ALS with Alzheimer’s and Parkinson’s
The effort in the iidentification of the genes responsible for amyotrophic lateral sclerosis (SLA) takes a step forward thanks to international collaboration: the results achieved have been published on Nature Genetics. The “genome-wide or GWA” study made it possible to evaluate all the genes of an individual at the same time: the DNA of 29,612 patients with ALS in “sporadic form”, the most common form of the disease, and 122,656 healthy subjects were analyzed , with the identification of 15 gene variants associated with the disease. These variants affect genes involved in specific metabolic pathways, and also related to neurodegenerative processes of other diseases, such as vesicular transport mechanisms between Golgi apparatus and endoplasmic reticulum, autophagy with evidence of primitive involvement of glutamatergic motor neuron cells.
I study
The study is the result of a international collaboration led by Jan Veldink of Utrec Universityht,
in Holland which was attended by institutions from all over the world. Among the Italian research groups, the Neuroscience Laboratory and Neurology Unit of the Italian Auxological Institute IRCCS which supported the research together with the University of Milan and the Dino Ferrari Center. The group includes Isabella Fogh, Nicola Ticozzi and Antonia Ratti of the University of Milan, coordinated by Vincenzo Silani. “The recent study – explains Silani, Professor of Neurology at the University of Milan, head of neurology at Auxologico San Luca in Milan and founder of the Italian Consortium SLAGEN – confirmed, among the 15 loci associated with the disease, 8 genes already identified in previous studies further proving the respective pathogenetic involvement. Of particular importance, however, is theidentification of 7 new loci that contribute to better delineate the disease-specific neurodegeneration mechanisms. The study demonstrates, in fact, the expression of genes implicated in particular in glutamatergic motor neurons, thus suggesting that the neurodegenerative process in ALS is originally borne by the neuronal cell and not microglial or astrocytic. In particular, the role of both vesicle transport and autophagy is demonstrated as a determinant of neuronal loss with particular involvement of the Golgi complex and the endoplasmic reticulum.
Links with other neurodegenerative diseases
“Lastly – explained Silani – elevated cholesterol levels appear to play a causal role for ALS as will be further underlined by an outgoing work by the same group “.
Very interesting is the csharing of pathogenetic genes reported with other neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, corticobasal degeneration, progressive supranuclear palsy and frontotemporal dementia further validating the assumption of common pathogenetic mechanisms for various neurodegenerative diseases. “This study – concludes Silani – differs from the previous ones due to the large number of patients analyzed and for the completeness of information obtained with the inclusion of ALS alongside other neurodegenerative diseases because they share common pathogenetic mechanisms with the indication of a primitive neuronal process at the origin of the disease, thus reinforcing the concept of a selective vulnerability of the motor neuron cell in ALS “.
Common mechanisms
The effort of Silani’s group, which began in 2014 with a first study by GWA on a large series of ALS patients, is now strengthened with this new work aimed at identifying genes and pathogenetic mechanisms of ALS, in the context of other neurodegenerative diseases. The perspective of being able to act on shared mechanisms between different pathologies constitutes the prerequisite for a therapeutic alliance aimed at rapidly defining effective therapeutic approaches, it being understood that the target remains the spinal motor neuron responsible for the biological graft of the disease
December 9, 2021 (change December 9, 2021 | 11:22)
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