GLUT-1 changes in paediatric Huntington disease brain cortex and fibroblasts: an observational case-control study

Tramutola, Antonella; Bakels, Hannah S.; Perrone, Federica; Di Nottia, Michela; Mazza, Tommaso; Abruzzese, Maria Pia; Zoccola, Martina; Pagnotta, Sara; Carrozzo, Rosalba; de Bot, Susanne T.; Perluigi, Marzia; van Roon-Mom, Willeke M.C.; Squitieri, Ferdinando

doi:10.1016/j.ebiom.2023.104849

Cited by 8 publications

(2 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mitochondria are crucial for energy metabolism and their proteins are encoded by both nDNA and mtDNA. mtDNA damage has been described in the brain of HD mouse models [ 120 , 121 ], adult HD [ 122 , 123 ], and pediatric HD patients [ 124 ]. Moreover, nDNA and mtDNA alterations have been reported also in peripheral tissues, suggesting a possible role as easily accessible biomarkers of disease progression and therapeutic monitoring.…”

Section: Mitochondrial Mutationsmentioning

confidence: 99%

Beyond CAG Repeats: The Multifaceted Role of Genetics in Huntington Disease

Pengo,

Squitieri

2024

Genes

Self Cite

View full text Add to dashboard Cite

Huntington disease (HD) is a dominantly inherited neurodegenerative disorder caused by a CAG expansion on the huntingtin (HTT) gene and is characterized by progressive motor, cognitive, and neuropsychiatric decline. Recently, new genetic factors besides CAG repeats have been implicated in the disease pathogenesis. Most genetic modifiers are involved in DNA repair pathways and, as the cause of the loss of CAA interruption in the HTT gene, they exert their main influence through somatic expansion. However, this mechanism might not be the only driver of HD pathogenesis, and future studies are warranted in this field. The aim of the present review is to dissect the many faces of genetics in HD pathogenesis, from cis- and trans-acting genetic modifiers to RNA toxicity, mitochondrial DNA mutations, and epigenetics factors. Exploring genetic modifiers of HD onset and progression appears crucial to elucidate not only disease pathogenesis, but also to improve disease prediction and prevention, develop biomarkers of disease progression and response to therapies, and recognize new therapeutic opportunities. Since the same genetic mechanisms are also described in other repeat expansion diseases, their implications might encompass the whole spectrum of these disorders.

show abstract

Section: Mitochondrial Mutationsmentioning

confidence: 99%

Beyond CAG Repeats: The Multifaceted Role of Genetics in Huntington Disease

Pengo,

Squitieri

2024

Genes

Self Cite

View full text Add to dashboard Cite

show abstract

“…There is a need to understand energy metabolism dysfunction in Huntington's disease, both at whole body and cellular level. Even though Tramutola and colleagues present a study limited to two patients with paediatric Huntington's disease, 8 the study highlights the potential of juvenile Huntington's disease as a source of knowledge that can guide future studies relevant for adult Huntington's disease as well. The metabolic alterations found in Huntington's disease are subtle and progress slowly, contributing to the difficulties to pin-point metabolic dysfunction.…”

mentioning

confidence: 99%

Centrally and peripherally altered glucose transporters: is it time to revisit energy deficiency as a potential treatment strategy in Huntington's disease?

Björkqvist

2023

eBioMedicine

View full text Add to dashboard Cite

Pediatric Huntington Disease Brains Have Distinct Morphologic and Metabolic Traits: the RAREST‐JHD Study

Caligiuri,

Tinelli,

Vizza

et al. 2024

Movement Disord Clin Pract

View full text Add to dashboard Cite

BackgroundPediatric‐onset Huntington's disease (POHD) exhibits a phenotype different from adult‐onset HD (AOHD), with hypokinetic movement disorders (eg, rigidity, bradykinesia, and dystonia) rather than chorea typical of AOHD.ObjectivesThe aim was to identify pathophysiology‐based biomarkers specific to POHD (≥60 CAG repeats).MethodsSimultaneous hybrid imaging using [18F]fluoro‐2‐deoxy‐d‐glucose (FDG) positron emission tomography plus magnetic resonance imaging (FDG‐PET/MRI) and clinical assessment using standardized Huntington's disease (HD) scales were employed. Exploratory longitudinal analyses were also performed.ResultsStriatal volume loss was remarkable and more severe in POHD (n = 5) than in AOHD (n = 14). Widespread, significantly altered glucose metabolism occurred in several different POHD cortical areas and thalamus, but not AOHD cortex, consistent with differences in clinical progression.ConclusionsPOHD patients' brains exhibited distinct morphologic and metabolic traits compared to AOHD patients’ brains, with longitudinal changes mirroring clinical progression. Hybrid FDG‐PET/MRI highlighted a variable regional brain dysfunction in vivo, as a biological consequence of highly expanded CAG repeats. Findings provide further evidence that POHD is a distinct disease from AOHD.

show abstract

GLUT-1 changes in paediatric Huntington disease brain cortex and fibroblasts: an observational case-control study

Cited by 8 publications

References 31 publications

Beyond CAG Repeats: The Multifaceted Role of Genetics in Huntington Disease

Beyond CAG Repeats: The Multifaceted Role of Genetics in Huntington Disease

Centrally and peripherally altered glucose transporters: is it time to revisit energy deficiency as a potential treatment strategy in Huntington's disease?

Pediatric Huntington Disease Brains Have Distinct Morphologic and Metabolic Traits: the RAREST‐JHD Study

Contact Info

Product

Resources

About