Polyglutamine
(polyQ) diseases, such as Huntington’s disease
and several types of spinocerebellar ataxias, are dominantly inherited
progressive neurodegenerative disorders and characterized by the presence
of expanded CAG trinucleotide repeats in the respective
disease locus of the patient genomes. Patients with polyQ diseases
currently need to rely on symptom-relieving treatments because disease-modifying
therapeutic interventions remain scarce. Many disease-modifying therapeutic
agents are now under clinical testing for treating polyQ diseases,
but their delivery to the brain is often too invasive (e.g., intracranial
injection) or inefficient, owing to in vivo degradation
and clearance by physiological barriers (e.g., oral and intravenous
administration). Nanoparticles provide a feasible solution for improving
drug delivery to the brain, as evidenced by an increasing number of
preclinical studies that document the efficacy of nanomedicines for
polyQ diseases over the past 5–6 years. In this review, we
present the pathogenic mechanisms of polyQ diseases, the common animal
models of polyQ diseases for evaluating the efficacy of nanomedicines,
and the common administration routes for delivering nanoparticles
to the brain. Next, we summarize the recent preclinical applications
of nanomedicines for treating polyQ diseases and improving neurological
conditions in vivo, placing emphasis on antisense
oligonucleotides, small peptide inhibitors, and small molecules as
the disease-modifying agents. We conclude with our perspectives of
the burgeoning field of “nanomedicines for polyQ diseases”,
including the use of inorganic nanoparticles and potential drugs as
next-generation nanomedicines, development of higher-order animal
models of polyQ diseases, and importance of “brain-nano”
interactions.
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