Diet and Nutrients in Rare Neurological Disorders: Biological, Biochemical, and Pathophysiological Evidence

Abstract

Background/Objectives: Rare diseases are a wide and heterogeneous group of multisystem life-threatening or chronically debilitating clinical conditions with reduced life expectancy and a relevant mortality rate in childhood. Some of these disorders have typical neurological symptoms, presenting from birth to adulthood. Dietary patterns and nutritional compounds play key roles in the onset and progression of neurological disorders, and the impact of alimentary needs must be enlightened especially in rare neurological diseases. This work aims to collect the in vitro, in vivo, and clinical evidence on the effects of diet and of nutrient intake on some rare neurological disorders, including some genetic diseases, and rare brain tumors. Herein, those aspects are critically linked to the genetic, biological, biochemical, and pathophysiological hallmarks typical of each disorder. Methods: By searching the major web-based databases (PubMed, Web of Science Core Collection, DynaMed, and Clinicaltrials.gov), we try to sum up and improve our understanding of the emerging role of nutrition as both first-line therapy and risk factors in rare neurological diseases. Results: In line with the increasing number of consensus opinions suggesting that nutrients should receive the same attention as pharmacological treatments, the results of this work pointed out that a standard dietary recommendation in a specific rare disease is often limited by the heterogeneity of occurrent genetic mutations and by the variability of pathophysiological manifestation. Conclusions: In conclusion, we hope that the knowledge gaps identified here may inspire further research for a better evaluation of molecular mechanisms and long-term effects.

Keywords: dietary pattern; neurodegenerative disease; nutritional compounds; orphan disease; rare leukodystrophy; rare neurological disorders; rare tumors.

Figure 1

Main characteristics of rare neurological diseases and possible investigations for symptomatic treatments (created with BioRender.com, accessed on 3 September 2024).

Figure 2

Factors that influence alimentary wellness by modulator effects on the main homeostatic functions (created with BioRender.com, accessed on 27 June 2024).

Figure 3

In vitro models as tools in rare neurological disease research and therapeutic development (partially created with BioRender.com, accessed on 7 August 2024).

Figure 4

Animal models for rare neurological diseases (created with BioRender.com, accessed on 3 September 2024).

Figure 5

MeCP2 gene structure and its activity on target genes. The meCP2 gene has N-terminal (NTD); methyl binding (MBD); intervening (ID); transcription repression (TRD); and C-terminal (CTD) domains. MeCP2 recruits a transcriptional corepressor complex containing Sin3A and histone deacetylase (HDAC) to methylated CpG islands and induces transcription inhibition in the target gene (TRD, transcriptional repression domain; MBD, methyl-CpG-binding domain). MeCP2 can activate gene transcription by recruiting CREB and other transcriptional factors to non-methylated CG DNA regions (partially created with BioRender.com, accessed on 10 August 2024).