Mitochondrial Neurodegenerative Diseases: Three Mitochondrial Ribosomal Proteins as Intermediate Stage in the Pathway That Associates Damaged Genes with Alzheimer’s and Parkinson’s

SIMPLE SUMMARY: Neurodegenerative diseases are characterized by the progressive degeneration of nerve cells. Some neurodegenerative diseases such as Alzheimer’s and Parkinson’s are caused by disorders in the mitochondria, which are organelles present in the eukaryotic cells of animals, plants and fungi, and their function is to produce energy. The formation and function of mitochondria are influenced by two separate genetic inheritances physically and functionally present in the cell: nuclear DNA, which provides 90% of key components such as proteins, and mitochondrial DNA, which provides 5% of these components. Recently, three genes in the nuclear DNA have been identified that encode for three mitochondrial ribosomal proteins, namely MRPL44, NAM9 and GEP3, respectively. The absence of or defects in these proteins could potentially be the cause of neurodegenerative diseases such as Alzheimer’s and Parkinson’s. In this review, we present the recent advances in the most common mitochondrial neurodegenerative diseases, the mitochondrial ribosomal proteins associated with mitochondrial neurodegenerative diseases and the aforementioned three ribosomal proteins. Finally, we evaluate our experimental hypothesis useful for the characterization of these three ribosomal proteins in order to understand their role in mitochondrial neurodegenerative dysfunctions, which could lead to the development of potential therapeutic drugs for the treatment of such diseases. ABSTRACT: Currently, numerous research endeavors are dedicated to unraveling the intricate nature of neurodegenerative diseases. These conditions are characterized by the gradual and progressive impairment of specific neuronal systems that exhibit anatomical or physiological connections. In particular, in the last twenty years, remarkable efforts have been made to elucidate neurodegenerative disorders such as Alzheimer′s disease and Parkinson′s disease. However, despite extensive research endeavors, no cure or effective treatment has been discovered thus far. With the emergence of studies shedding light on the contribution of mitochondria to the onset and advancement of mitochondrial neurodegenerative disorders, researchers are now directing their investigations toward the development of therapies. These therapies include molecules designed to protect mitochondria and neurons from the detrimental effects of aging, as well as mutant proteins. Our objective is to discuss and evaluate the recent discovery of three mitochondrial ribosomal proteins linked to Alzheimer′s and Parkinson′s diseases. These proteins represent an intermediate stage in the pathway connecting damaged genes to the two mitochondrial neurological pathologies. This discovery potentially could open new avenues for the production of medicinal substances with curative potential for the treatment of these diseases.