Molecular Mechanisms in the Design of Novel Targeted Therapies for Neurodegenerative Diseases

Abstract

Neurodegenerative diseases are a diverse group of diseases characterized by a progressive loss of neurological function due to damage to nerve cells in the central nervous system. In recent years, there has been a worldwide increase in the expanding associated with increasing human life expectancy. Molecular mechanisms control many of the essential life processes of cells, such as replication, transcription, translation, protein synthesis and gene regulation. These are complex interactions that form the basis for understanding numerous processes in the organism and developing new diagnostic and therapeutic approaches. In the context of neurodegenerative diseases, molecular basis refers to changes at the molecular level that cause damage to or degeneration of nerve cells. These may include protein aggregates leading to pathological structures in brain cells, impaired protein transport in nerve cells, mitochondrial dysfunction, inflammatory processes or genetic mutations that impair nerve cell function. New medical therapies are based on these mechanisms and include gene therapies, reduction in inflammation and oxidative stress, and the use of miRNAs and regenerative medicine. The aim of this study was to bring together the current state of knowledge regarding selected neurodegenerative diseases, presenting the underlying molecular mechanisms involved, which could be potential targets for new forms of treatment.

Keywords: Alexander disease; Huntington disease; amyotrophic lateral sclerosis; central nervous system; molecular mechanisms; multiple sclerosis; neurodegenerative diseases; spinal muscular atrophy.

Figure 1

Pathological cellular processes in ALS. Mutations in ALS-associated genes lead to mutated RNA-binding proteins and damage to cellular and mitochondrial transport. Protein aggregation and mitochondrial mutations lead to energy disturbances and increased oxidative stress [13,16,23]. The figure was partly generated using Servier Medical Art, provided by Servier and licensed under a Creative Commons Attribution 4.0 unported license.

Figure 2

Alexander disease: symptoms occurring during a particular period of life. The figure was partly generated using Servier Medical Art, provided by Servier and licensed under a Creative Commons Attribution 4.0 unported license.

Figure 3

Molecular mechanisms of spinal muscular atrophy development. Wild-type chromosome 5q13 is covered by the telomeric SMN1 gene and the centromeric SMN2 gene (A); splicing pre-mRNA SMN1 produces full-length mRNA (B); exon 7 splicing in SMN1 and SMN2 genes (C). Reprinted with permission from Ref. [87]. Copyright 2022 MDPI.