Relationship of Mediterranean Diet and Caloric Intake to Phenoconversion in Huntington Disease

Marder, Karen; Gu, Yian; Eberly, Shirley; Tanner, Caroline M.; Scarmeas, Nikolaos; Oakes, David; Shoulson, Ira

doi:10.1001/jamaneurol.2013.3487

Cited by 26 publications

(30 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This may be due to a lower level of urate, which leads to a faster progression and manifestation of HD. These types of diet-related studies need further investigation [84,107,126]. Intermittent fasting promotes autophagy and cleared the mHTT [127].…”

Section: Dietmentioning

confidence: 99%

Therapeutic Advances for Huntington’s Disease

et al. 2020

View full text Add to dashboard Cite

Huntington’s disease (HD) is a progressive neurological disease that is inherited in an autosomal fashion. The cause of disease pathology is an expansion of cytosine-adenine-guanine (CAG) repeats within the huntingtin gene (HTT) on chromosome 4 (4p16.3), which codes the huntingtin protein (mHTT). The common symptoms of HD include motor and cognitive impairment of psychiatric functions. Patients exhibit a representative phenotype of involuntary movement (chorea) of limbs, impaired cognition, and severe psychiatric disturbances (mood swings, depression, and personality changes). A variety of symptomatic treatments (which target glutamate and dopamine pathways, caspases, inhibition of aggregation, mitochondrial dysfunction, transcriptional dysregulation, and fetal neural transplants, etc.) are available and some are in the pipeline. Advancement in novel therapeutic approaches include targeting the mutant huntingtin (mHTT) protein and the HTT gene. New gene editing techniques will reduce the CAG repeats. More appropriate and readily tractable treatment goals, coupled with advances in analytical tools will help to assess the clinical outcomes of HD treatments. This will not only improve the quality of life and life span of HD patients, but it will also provide a beneficial role in other inherited and neurological disorders. In this review, we aim to discuss current therapeutic research approaches and their possible uses for HD.

show abstract

Section: Dietmentioning

confidence: 99%

Therapeutic Advances for Huntington’s Disease

et al. 2020

View full text Add to dashboard Cite

show abstract

“…A handful of environmental modulators have been correlated with age of onset in HD patients based on retrospective questionnaire studies (Buruma et al, 1987;López-Sendón et al, 2011;Marder et al, 2013;Marder et al, 2009;Simonin et al, 2013;Trembath et al, 2010). For example, Trembath et al found that a premorbid lifestyle of activities lacking in physical or intellectual challenge (a passive lifestyle) was correlated with an earlier age of onset in HD, independent of CAG repeat length.…”

Section: Accepted Manuscript Introductionmentioning

confidence: 99%

High stress hormone levels accelerate the onset of memory deficits in male Huntington's disease mice

Mo¹,

Pang²,

Ransome³

et al. 2014

Neurobiology of Disease

View full text Add to dashboard Cite

Huntington's disease (HD) is a neurodegenerative disorder caused by a tandem repeat mutation in the huntingtin gene. Lifestyle factors, such as lack of activity may contribute to the variability in the age of disease onset. Therefore, better understanding of environmental modifiers may uncover potential therapeutic approaches to delay disease onset and progression. Recent data suggest that HD patients and transgenic mouse models show a dysregulated stress response. In this present study, we elevated stress hormone levels through oral corticosterone (CORT) treatment and assessed its impact on the development of motor impairment and cognitive deficits using the R6/1 transgenic mouse model of HD. We found that CORT consumption did not alter rotarod performance of R6/1 HD or wild-type (WT) littermates. However, the onset of hippocampal-dependent Y-maze deficits was accelerated in male R6/1 mice by 5days of CORT treatment, whereas short term memory of WT and female R6/1 mice was unaffected. We then further investigated the male HD susceptibility to CORT by measuring TrkB activation, BDNF and glucocorticoid receptor expression as well as the level of cell proliferation in the hippocampus. CORT treatment increased the levels of phosphorylated TrkB in male R6/1 mice only. There were no effects of CORT on hippocampal BDNF protein or mRNA levels; nor on expression of the glucocorticoid receptors in any group. Hippocampal cell proliferation was decreased in male R6/1 mice and this was further reduced in CORT-drinking male R6/1 mice. Female mice (WT and R6/1) appeared to be protected from the impacts of CORT treatment in all our hippocampal measures. Overall, our data demonstrate that treatment with corticosterone is able to modulate the onset of HD symptomatology. We present the first evidence of a male-specific vulnerability to stress impacting on the development of short-term memory deficits in HD. More generally, we found that female mice were protected from the detrimental effects of CORT treatment on a variety of hippocampus-based measures. Hippocampal plasticity and memory in HD may be more susceptible to the impacts of stress in a sex-dependent manner. We propose clinical investigations of stress as a key environmental modifier of HD symptom onset.

show abstract

“…This may be due to a lower level of urate, which leads to a faster progression and manifestation of HD. These types of diet-related studies need further investigation [95,118,142]. (Table 1 & Fig.…”

Section: Dietmentioning

confidence: 99%

Therapeutics Advancement for Huntington Disease

Kumar¹,

Kumar²,

Singh³

et al. 2019

Preprint

View full text Add to dashboard Cite

Huntington disease (HD) is an autosomal dominantly inherited fatal neurodegenerative disease. It affects motor, cognitive and psychiatric functions, and ultimately leads to death. The pathology of the disease is due to an expansion of CAG repeats in exon 1 of the huntingtin gene on chromosome 4, which produces a mutant huntingtin protein (mhtt). HD patients manifest a typical phenotype of sporadic, rapid, involuntary control of limb movement, stiffness of limbs, impaired cognition and severe psychiatric disturbances. A variety of symptomatic treatments (which target excitotoxicity, the dopamine pathway, caspases, aggregation, mitochondrial dysfunction, transcriptional dysregulation, mHtt, nucleic acid, neurodegeneration, fetal neural transplants, etc.) are currently available, and new symptomatic and potentially disease-modifying therapies are being actively developed. Recent advances in novel therapeutic strategies, including targeting mutant huntingtin (mhtt) and the htt gene, promise another wave of disease-modifying trials in the near future. A better appreciation of heterogeneous clinical phenomenology and immediate tractable treatment goals coupled with advances in new therapeutics heralds a golden age of HD treatment that will positively impact the quality of life and longevity of HD patients and inform advances in other inherited and neurodegenerative neurological disorders. In the present review literature, our aims to address the latest research on promising therapeutics based on influencing the hypothesized pathological mechanisms associated with HD.

show abstract

Relationship of Mediterranean Diet and Caloric Intake to Phenoconversion in Huntington Disease

Cited by 26 publications

References 39 publications

Therapeutic Advances for Huntington’s Disease

Therapeutic Advances for Huntington’s Disease

High stress hormone levels accelerate the onset of memory deficits in male Huntington's disease mice

Therapeutics Advancement for Huntington Disease

Contact Info

Product

Resources

About