Mitochondrial Dysfunction in Down Syndrome: From Pathology to Therapy.

Area of Science:

• Genetics
• Cell Biology
• Biochemistry

Background:

• Mitochondrial dysfunction is observed in Down syndrome (DS), associated with trisomy of chromosome 21 (HSA21).
• Mitochondria are vital for cellular energy production, calcium homeostasis, and programmed cell death, regulated by nuclear and mitochondrial genes.
• HSA21 contains genes influencing oxidative phosphorylation (OXPHOS) and mitochondrial regulation.

Purpose of the Study:

• To review HSA21 dosage-sensitive nuclear-encoded mitochondrial genes and their role in DS phenotypes.
• To discuss impaired mitochondrial dynamics, structural defects, and bioenergetic dysregulation in DS.
• To explore therapeutic strategies targeting mitochondrial function in DS.

Main Methods:

• Literature review focusing on HSA21 genes, mitochondrial function, and DS.
• Analysis of overexpression-related phenotypes linked to HSA21 gene dosage.
• Examination of therapeutic approaches including gene therapy and pharmacological interventions.

Main Results:

• Overexpression of HSA21 genes leads to impaired mitochondrial dynamics and structural defects.
• DS exhibits OXPHOS deficiency and reduced ATP production due to dysregulated mitochondrial bioenergetics.
• Therapeutic interventions can modulate mitochondrial function and reduce oxidative stress in DS.

Conclusions:

• Targeting mitochondrial biogenesis and function presents a feasible strategy for improving DS pathophysiology.
• Modulating cellular energy deficits through mitochondrial interventions may enhance quality of life for individuals with DS.