Huntington’s disease (HD) is a rare hereditary autosomal dominant neurodegenerative disorder, which is caused by expression of mutant huntingtin protein (mHTT) with an abnormal number of glutamine repeats in its N terminus, and characterized by intracellular mHTT aggregates (inclusions) in the brain. Exosomes are small extracellular vesicles that are secreted generally by all cell types and can be isolated from almost all body fluids such as blood, urine, saliva, and cerebrospinal fluid. Exosomes may participate in the spreading of toxic misfolded proteins across the central nervous system in neurodegenerative diseases. In HD, such propagation of mHTT was observed both in vitro and in vivo. On the other hand, exosomes might carry molecules with neuroprotective effects. In addition, due to their capability to cross blood-brain barrier, exosomes hold great potential as sources of biomarkers available from periphery or carriers of therapeutics into the central nervous system. In this review, we discuss the emerging roles of exosomes in HD pathogenesis, diagnosis, and therapy.

(1) Background: Huntington’s disease (HD) is rare incurable hereditary neurodegenerative disorder caused by CAG repeat expansion in the gene coding for the protein huntingtin (HTT). Mutated huntingtin (mHTT) undergoes fragmentation and accumulation, affecting cellular functions and leading to neuronal cell death. Porcine models of HD are used in preclinical testing of currently emerging disease modifying therapies. Such therapies are aimed at reducing mHTT expression, postpone the disease onset, slow down the progression, and point out the need of biomarkers to monitor disease development and therapy efficacy. Recently, extracellular vesicles (EVs), particularly exosomes, gained attention as possible carriers of disease biomarkers. We aimed to characterize HTT and mHTT forms/fragments in blood plasma derived EVs in transgenic (TgHD) and knock-in (KI-HD) porcine models, as well as in HD patients’ plasma. (2) Methods: Small EVs were isolated by ultracentrifugation and HTT forms were visualized by western blotting. (3) Results: The full length 360 kDa HTT co-isolated with EVs from both the pig model and HD patient plasma. In addition, a ~70 kDa mutant HTT fragment was specific for TgHD pigs. Elevated total huntingtin levels in EVs from plasma of HD groups compared to controls were observed in both pig models and HD patients, however only in TgHD were they significant (p = 0.02). (4) Conclusions: Our study represents a valuable initial step towards the characterization of EV content in the search for HD biomarkers.

Coppicing consists of periodically cutting back tree stems to ground level to stimulate the growth of multiple stems from the stool. In Central Europe, many coppiced forests were abandoned at the beginning of the last century owing to a decline in the demand for charcoal and wood. This was assumed to enable the forests to recover and the properties to become similar to those of unmanaged forest (high forest). Most studies on abandoned coppiced forest have focused on forest recovery, while soil recovery has generally been overlooked. With the aim of filling this gap, this study investigated the effect of coppicing abandonment on soil recovery by analysing the changes in soil enzyme activities (dehydrogenase, ß-glucosidase, invertase, urease, acid phosphatase and arylsulphatase). Two differently managed sessile oak (Quercus petraea) forests were selected for study: a former coppice forest, abandoned more than 90 years ago, and an undisturbed forest. The analytical data were compared to assess the degree of recovery of the soil in the abandoned coppice forest. The soil organic matter content was two times lower in the abandoned coppice than in the high forest, suggesting that organic matter depletion due the past coppicing is a long-term effect. All of the absolute enzyme activities were also two times lower in the abandoned coppice forest soil than in the high forest soil. However, the specific enzyme activities were similar in both types of soil. This indicates that metabolic activity is similar in both soil types, suggesting that it either recovers faster than organic matter and soil enzyme activity or that, despite the depletion in organic matter and enzyme activities, metabolic activity was sustained in coppiced forest soil. However, in the latter case this would imply that organic matter and soil enzymes were lost in exactly the same proportion, which is highly improbable.