Huntington\'s disease (HD), a rare autosomal dominant neurodegenerative disease, causes the gradual deterioration of neurons in the basal ganglia, specifically in the striatum. HD displays a wide range of symptoms, from motor disturbances such as chorea, dystonia, and bradykinesia to more debilitating symptoms such as cognitive decline, behavioral abnormalities, and psychiatric disturbances. Current research suggests the potential use of dietary interventions as viable strategies for slowing the progression of HD. Most notably, the Mediterranean, vegan, carnivore, paleo, and ketogenic diets have gained attention due to their hypothesized impact on neuroprotection and symptomatic modulation in various neurodegenerative disorders. Despite substantial nutritional differences among these diets, they share a fundamental premise-that dietary factors have an influential impact in modifying pertinent biological pathways linked to neurodegeneration. Understanding the intricate interactions between these dietary regimens and HD pathogenesis could open avenues for personalized interventions tailored to the individual\'s specific needs and genetic background. Ultimately, elucidating the multifaceted effects of these diets on HD offers a promising framework for developing comprehensive therapeutic approaches that integrate dietary strategies with conventional treatments.

BACKGROUND: Although Huntington\'s disease (HD) is usually thought of as a triad of motor, cognitive, and psychiatric symptoms, there is growing appreciation of HD as a systemic illness affecting the entire body.
OBJECTIVE: This review aims to draw attention to these systemic non-motor symptoms in HD.
METHODS: We identified relevant studies published in English by searching MEDLINE (from 1966 to September 2023), using the following subject headings: Huntington disease, autonomic, systemic, cardiovascular, respiratory, gastrointestinal, urinary, sexual and cutaneous, and additional specific symptoms.
RESULTS: Data from 123 articles were critically reviewed with focus on systemic features associated with HD, such as cardiovascular, respiratory, gastrointestinal, urinary, sexual and sweating.
CONCLUSIONS: This systematic review draws attention to a variety of systemic and autonomic co-morbidities in patients with HD. Not all of them correlate with the severity of the primary HD symptoms or CAG repeats. More research is needed to better understand the pathophysiology and treatment of systemic and autonomic dysfunction in HD.

Huntington\'s disease (HD) is an autosomal dominant disease caused by an abnormally high number of CAG repeats at the huntingtin-encoding gene, HTT. This genetic alteration results in the expression of a mutant form of the protein (mHTT) and the formation of intracellular aggregates, inducing an inflammatory state within the affected areas. This dysfunction of inflammatory response leads to elevated levels of related inflammatory markers in both CNS tissue samples and body fluids. This study aims to investigate peripheral/blood concentrations of inflammatory molecules in HD.
A search was conducted in MEDLINE, Scopus, Web of Science, and Embase databases until March 30th, 2023. Random-effect meta-analysis was used for exploring concentrations of inflammatory molecules in HD. Subgroup and sensitivity analyses were used to assess heterogeneity among the included studies. The study protocol has been registered in PROSPERO with the ID number CRD42022296078.
Ten studies were included in the meta-analysis. Plasma levels of Interleukin 6 (IL-6) and IL-10 were higher in HD compared to controls. Other biomarkers, namely, complement component C-reactive protein (CRP), C3, interferon-γ (IFN-γ), IL-1, IL-2, IL-8, and tumor necrosis factor-α (TNF-α), did not show any significant differences between the two groups. In addition, the subgroup analysis results established no significant differences in levels of these biomarkers in body fluids among premanifest and manifest HD patients.
The results of this study provide evidence for the presence of higher plasma levels of IL-6 and IL-10 in HD patients in comparison with healthy controls.

Huntington\'s disease (HD) is a rare, inherited disorder with a broad spectrum of manifestations that vary with disease severity and progression. Although genetic testing can readily confirm the initial diagnosis of HD, markers sensitive to HD progression are needed to aid the development of individual treatment plans. The current analysis aims to identify plasma Interleukin-6 (IL-6) as a marker of disease progression in HD patients. A systematic search of PubMed and Medline from conception through October 2021 was conducted. Studies reporting plasma IL-6 levels of mutation-positive HD patients and healthy controls that met inclusion criteria were selected. The search strategy collected 303 studies, 9 of which met analysis inclusion criteria. From included studies, plasma IL-6 levels of 469 individuals with the HD mutation and 206 healthy controls were collected. Plasma IL-6 levels were meta-analytically compared between healthy controls and individuals with the confirmed HD mutation at all stages of disease and correlated to performance on standardized measures of total cognitive and motor function. Plasma IL-6 was significantly increased in HD groups compared to controls (g = 0.73, 95% CI = 0.31,1.16, P < 0.01) and increased significantly throughout most stages of disease progression, notably between pre-manifest and manifest (g = 0.31, 95% CI = 0.04,0.59, P < 0.05) and early and moderate HD stages (g = 0.52, 95% CI = 0.18,0.86, P < 0.01). Significant correlations between plasma IL-6 levels and HD symptomatic progression were identified, with increased cytokine levels associated with more severe motor impairments (r = 0.179, 95% CI = 0.0479,0.304, P = 0.008) and more extreme disabilities in activities of daily living and/or work tasks (r = -0.229, 95% CI = -0.334, -0.119, P < 0.001). Conclusively, plasma IL-6 levels correlate with disease and motor symptom progression and may act as a viable marker for clinical use. Analysis is limited by small study numbers and highlights the need for future work to identify definitive ranges or rates of change of plasma IL-6 levels that correlate to progressive HD disease states.

Stem cells have been the subject of research for years due to their enormous therapeutic potential. Most neurological diseases such as multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Alzheimer\'s disease (AD), Parkinson\'s disease (PD), and Huntington\'s disease (HD) are incurable or very difficult to treat. Therefore new therapies are sought in which autologous stem cells are used. They are often the patient\'s only hope for recovery or slowing down the progress of the disease symptoms. The most important conclusions arise after analyzing the literature on the use of stem cells in neurodegenerative diseases. The effectiveness of MSC cell therapy has been confirmed in ALS and HD therapy. MSC cells slow down ALS progression and show early promising signs of efficacy. In HD, they reduced huntingtin (Htt) aggregation and stimulation of endogenous neurogenesis. MS therapy with hematopoietic stem cells (HSCs) inducted significant recalibration of pro-inflammatory and immunoregulatory components of the immune system. iPSC cells allow for accurate PD modeling. They are patient-specific and therefore minimize the risk of immune rejection and, in long-term observation, did not form any tumors in the brain. Extracellular vesicles derived from bone marrow mesenchymal stromal cells (BM-MSC-EVs) and Human adipose-derived stromal/stem cells (hASCs) cells are widely used to treat AD. Due to the reduction of Aβ42 deposits and increasing the survival of neurons, they improve memory and learning abilities. Despite many animal models and clinical trial studies, cell therapy still needs to be refined to increase its effectiveness in the human body.

Huntington\'s disease (HD) is a neurodegenerative disorder characterized by severe motor, cognitive and psychiatric symptoms. Patients of all ages can present with a dysfunction of the nervous system, which leads to the progressive loss of movement control and disabilities in speech, swallowing, communications, etc. The molecular basis of the disease is well-known, as HD is related to a mutated gene, a trinucleotide expansion, which encodes to the huntingtin protein. This protein is linked to neurogenesis and the loss of its function leads to neurodegenerative disorders. Although the genetic cause of the disorder has been known for decades, no effective treatment is yet available to prevent onset or to eliminate the progression of symptoms. Thus, the present review focused on the development of novel methods for the timely and accurate diagnosis of HD in an aim to aid the development of therapies which may reduce the severity of the symptoms and control their progression. The majority of the therapies include gene-silencing mechanisms of the mutated huntingtin gene aiming to suppress its expression, and the use of various substances as drugs with highly promising results. In the present review, the latest approaches on the diagnosis of HD are discussed along with the need for genetic counseling and an up-to-date presentation of the applied treatments.

Huntington\'s disease (HD) is a hereditary, neurodegenerative disorder characterized by a triad of symptoms: motor, cognitive and psychiatric. HD is caused by a genetic mutation, expansion of the CAG repeat in the huntingtin gene, which results in loss of medium spiny neurons (MSNs) of the striatum. Cell replacement therapy (CRT) has emerged as a possible therapy for HD, aiming to replace those cells lost to the disease process and alleviate its symptoms. Initial pre-clinical studies used primary fetal striatal cells to provide proof-of-principal that CRT can bring about functional recovery on some behavioral tasks following transplantation into HD models. Alternative donor cell sources are required if CRT is to become a viable therapeutic option and human pluripotent stem cell (hPSC) sources, which have undergone differentiation toward the MSNs lost to the disease process, have proved to be strong candidates. The focus of this chapter is to review work conducted on the functional assessment of animals following transplantation of hPSC-derived MSNs. We discuss different ways that graft function has been assessed, and the results that have been achieved to date. In addition, this chapter presents and discusses challenges that remain in this field.

Neurodegenerative diseases are a class of incurable and debilitating diseases characterized by progressive degeneration and death of cells in the central nervous system. They have multiple underlying mechanisms; however, they all share common degenerative features, such as mitochondrial dysfunction. According to recent studies, neurodegenerative diseases are associated with the accumulation of dysfunctional mitochondria. Selective autophagy of mitochondria, called mitophagy, can specifically degrade excess or dysfunctional mitochondria within cells. In this review, we highlight recent findings on the role of mitophagy in neurodegenerative disorders. Multiple studies were collected, including those related to the importance of mitochondria, the mechanism of mitophagy in protecting mitochondrial health, and canonical and non-canonical pathways in mitophagy. This review elucidated the important function of mitophagy in neurodegenerative diseases, discussed the research progress of mitophagy in neurodegenerative diseases, and summarized the role of mitophagy-related proteins in neurological diseases. In addition, we also highlight pharmacological advances in neurodegeneration.

Huntington\'s disease (HD), an incurable, multi-generational, autosomal dominant disorder, creating unique challenges and a myriad of spiritually-related stressors in those affected and their familial caregivers. Spiritual suffering, experiences of grief/loss, and coping strategies have not been systematically studied in HD caregivers.
To comprehensively define spiritual suffering, grief/loss, and coping strategies used by HD caregivers.
A PRISMA-ScR scoping literature review was conducted. Data from included research articles were organized thematically using induction and open coding. A grounded, deductive approach was used to delineate a demarcated taxonomy of themes, which encompasses all three over-arching domains. Four reviewers, employing a modified Delphi approach, ascertained which themes were demonstrated by research participants in each study.
36 of 583 articles met the review criteria; none were published in the palliative care literature. Investigations primarily focused on intrapersonal (self-image) distress and existential angst; only rarely looking deeper into divine/transpersonal suffering, disrupted religious relationships, or meaning distress. HD caregivers experience profound grief/loss, expressed as disenfranchised grief that is associated with the ambiguous loss of their loved one, loss of family structure, social connectedness, and personal losses. Half of the studies reported maladaptive HD caregiver coping strategies-characterized by dysfunctional escape schemes; in contrast, transcendent/creative strategies were often unexplored.
HD caregivers experience prolonged grief and other forms of spiritual suffering as they progressively lose their loved ones and disruption to their own lives. With an improved assessment tool, teams with spiritual and palliative care experts will better be able to support HD family caregivers.

The Huntington\'s gene on chromosome 4 has a dominantly inherited CAG trinucleotide repeat expansion, ultimately resulting in Huntington\'s disease (HD), a completely penetrant neurological condition. The frequency is 10-100 times higher in the population descended from Europe than in East Asia. Through various processes, including impairment of proteostasis, transcription, and cell function, as well as direct toxicity of the mutant protein, mutated huntingtin triggers neuronal malfunction and loss at the cellular level. As the disease worsens, the brain becomes affected together with the striatum\'s initial macroscopic alterations. Since there are presently few medications that can change the course of the disease, palliative therapy, and symptom control are the cornerstone of treatment. Studying the cellular pathology and gross structural changes to the brain which occur as the illness advances have made enormous progress in recent years. There\'s been a substantial increase in medical studies and possible treatment options over the past ten years. The new treatments that aim to reduce amounts of mutant huntingtin are the most optimistic. However, one strategy is antisense oligonucleotide treatment, for which clinical trials are currently being conducted. These control trials might help us get another inch ahead of managing and perhaps even eliminating this nasty disease.