Protein/peptide aggregation is of fundamental importance in therapeutics because this type of event is related to pathologies of enormous social relevance, such as neurodegeneration. Interestingly, G-quadruplex (G4) DNA and RNA structures are also found in several neuropathies, and therefore ligands able to destabilize such nucleic acid secondary structures are envisaged to work as neurodrugs. In this Special Issue, we wish to focus on the more recent experimental and theoretical approaches for neurodrug design and development, with particular attention paid to the mechanisms of drug interference with protein and peptide aggregation pathways. However, contributions on G4 nucleic acid–drug interaction, G4 targets in neurodegenerative diseases, and nucleopeptide chemistry are also welcome, as they could improve the overall knowledge on the aggregation-based biochemistry at the interface between neurodrug design and therapy. Other themes of interest are inherent to the computational chemistry applied to G4, protein, and peptide science in the context of neuropathology therapy. This Special Issue is open to the submission of both original articles and reviews that describe research and ideas on themes treated in this issue for neurodegeneration-related molecular strategies.

Dr. Caterina Vicidomini
Dr. Giovanni N. Roviello
Guest Editors

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• proteins
• peptides
• amyloid
• Alzheimer disease
• Parkinson’s disease
• neurodrugs
• G-quadruplex nucleic acids
• biotechnology
• biomolecular targets
• peptide aggregation
• natural products
• synthetic drugs
• antiamyloid therapeutics

Title: Therapeutic strategies for spinocerebellar ataxia type 1
Authors: Laurie M.C. Kerkhof, Willeke M.C. van Roon-Mom, Ronald A.M. Buijsen
Affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands
Abstract: Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder which affects 1 to 2 per 100.000 individuals. The disease is caused by an extended CAG repeat in exon 8 of the ATXN1 gene and is characterized by a profound loss of cerebellar Purkinje cells leading to disturbances in balance and gait. At the moment, no curative treatment is available for SCA1. However, increasing knowledge on the neuropathological mechanisms and genetics of SCA1 has elucidated several therapeutic strategies that can potentially slow disease progression. SCA1 therapeutics can be classified into gene-, pharmacological and cell replacement therapies. These different therapeutic strategies either target the (mutant) ATXN1, the ataxin-1 protein, or pathways that play an important role in SCA1 disease pathology. In this review, we will provide a summary on the different therapeutic strategies that are currently being investigated for SCA1.