Alzheimer's disease (AD) is the most common form of dementia. During the recent decade, nanotechnology has been widely considered, as a promising tool, for theranosis (diagnosis and therapy) of AD. Here we first discuss pathophysiology and characteristics of AD with a focus on the amyloid cascade hypothesis. Then magnetic nanoparticles (MNPs) and recent works on their applications in AD, focusing on the superparamagnetic iron oxide nanoparticles (SPIONs), are reviewed. Furthermore, the amyloid−nanoparticle interaction is highlighted, with the scope to be highly considered by the scientists aiming for diagnostics and/or treatment of AD employing nanoparticles. Furthermore, recent findings on the "ignored" parameters (e.g., effect of protein "corona" at the surface of nanoparticles on amyloid-β (Aβ) fibrillation process) are discussed. KEYWORDS: Magnetic resonance imaging, SPION, amyloid-β, nanomedicine, nanotechnology A lzheimer's disease (AD) is named after Alois Alzheimer, who described the first case in a 55 year old female patient (i.e., Auguste Deter) in 1906. The description of Auguste's pathology was featured by lifelong deteriorating memory, speaking, physical, and social abilities. After her death, the autopsy revealed uniform brain atrophy, atherosclerosis changes in larger cerebral vessels, neuronal loss, and numerous small foci perceivable even without staining distributed over the entire cortex. It took over 70 years to reveal that those foci consist of aggregates of extracellular loads of small peptides called amyloid-β (Aβ), that are considered today one of the hallmarks of the disease. 1 AD is characterized by progressive deterioration of cognitive function, most commonly of memory, that increasingly interferes with patients' daily activities leading to loss of independency (for details, see http://www.alz.org/downloads/ facts_figures_2012.pdf). To date, no precise treatments have been clinically proven to avoid or prevent the progression of AD. Several different pharmacological agents can only ameliorate or provide temporary alleviation of the symptoms. 2 In this review, we introduce clinical aspects and characteristics of AD with a focus on the amyloid cascade hypothesis. Magnetic nanoparticles (MNPs), as promising theranosis tools, are introduced, and recent reports on the potential applications of superparamagnetic iron oxide nanoparticles (SPIONs) in AD are summarized. It is worthwhile to note that the SPIONs are known as promising theranosis candidates for AD, due to their biocompatibility, unique magnetic properties and multifunctional application capability. 3,4 The amyloid−nanoparticle interaction is highlighted, with the scope to be highly considered by the scientific community aiming for diagnostics and/or treatment of AD employing nanoparticles. Moreover, recent findings on the "ignored" parameters (e.g., the effect of protein "corona" at the surface of nanoparticles on Aβ fibrillation process) are discussed.

BackgroundPompe’s disease is a progressive myopathy caused by mutations in the lysosomal enzyme acid alphaglucosidase gene (GAA). A wide clinical variability occurs also in patients sharing the same GAA mutations, even within the same family.MethodsFor a large series of GSDII patients we collected some clinical data as age of onset of the disease, presence or absence of muscular pain, Walton score, 6-Minute Walking Test, Vital Capacity, and Creatine Kinase. DNA was extracted and tested for GAA mutations and some genetic polymorphisms able to influence muscle properties (ACE, ACTN3, AGT and PPARα genes).We compared the polymorphisms analyzed in groups of patients with Pompe disease clustered for their homogeneous genotype.ResultsWe have been able to identify four subgroups of patients completely homogeneous for their genotype, and two groups homogeneous as far as the second mutation is defined “very severe” or “potentially less severe”. When disease free life was studied we observed a high significant difference between groups. The DD genotype in the ACE gene and the XX genotype in the ACTN3 gene were significantly associated to an earlier age of onset of the disease. The ACE DD genotype was also associated to the presence of muscle pain.ConclusionsWe demonstrate that ACE and ACTN3 polymorphisms are genetic factors able to modulate the clinical phenotype of patients affected with Pompe disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-014-0102-z) contains supplementary material, which is available to authorized users.

Muscle quality is defined as muscle strength generated per unit muscle mass. If enzyme replacement therapy (ERT) has some effects on type II glycogenosis (GSDII) skeletal muscle pathology, we should be able to measure a change in strength and mass. We conducted a prospective study including 11 patients aged 54.2 ± 11.2 years, referring to a single institution and receiving ERT for ≥2 years. Median Walton score was 3 (2.5-6). Lower limb skeletal muscles were assessed by dynamometry and quantitative muscle MRI. Three segments (anterior thigh, posterior thigh, leg) were analysed separately. Clinical-MRI correlations were searched for at T0, T6/T8, and T18/24. Changes in lean and fat body composition were assessed by bioelectrical impedance analysis. We found that the anterior thigh showed the best therapeutic response, with an improvement in muscle quality (muscle mass: +7.5%, p = 0.035; strength: +45%, p = 0.002). BMI and lean body mass increased (p = 0.007). Patients with low BMI showed a better outcome. Intramuscular fat accumulation significantly progressed in spite of ERT (+3.7%, p = 0.001), especially in the poorly responsive posterior thigh muscles. Both clinical assessment and MRI revealed a definite improvement in the anterior thigh muscles. However, progression of intramuscular fat accumulation during ERT, as well as the limited responsiveness of posterior thigh muscles, suggests the necessity for early treatment intervention. The better outcome of patients with low BMI, if confirmed, may indicate that dietary protocols could be adopted as adjuvant measures to ERT in adult GSDII.

BackgroundPutative nucleotidyltransferase MAB21L1 is a member of an evolutionarily well-conserved family of the male abnormal 21 (MAB21)-like proteins. Little is known about the biochemical function of the protein; however, prior studies have shown essential roles for several aspects of embryonic development including the eye, midbrain, neural tube and reproductive organs.ObjectiveA homozygous truncating variant in MAB21L1 has recently been described in a male affected by intellectual disability, scrotal agenesis, ophthalmological anomalies, cerebellar hypoplasia and facial dysmorphism. We employed a combination of exome sequencing and homozygosity mapping to identify the underlying genetic cause in subjects with similar phenotypic features descending from five unrelated consanguineous families.ResultsWe identified four homozygous MAB21L1 loss of function variants (p.Glu281fs*20, p.Arg287Glufs*14 p.Tyr280* and p.Ser93Serfs*48) and one missense variant (p.Gln233Pro) in 10 affected individuals from 5 consanguineous families with a distinctive autosomal recessive neurodevelopmental syndrome. Cardinal features of this syndrome include a characteristic facial gestalt, corneal dystrophy, hairy nipples, underdeveloped labioscrotal folds and scrotum/scrotal agenesis as well as cerebellar hypoplasia with ataxia and variable microcephaly.ConclusionThis report defines an ultrarare but clinically recognisable Cerebello-Oculo-Facio-Genital syndrome associated with recessive MAB21L1 variants. Additionally, our findings further support the critical role of MAB21L1 in cerebellum, lens, genitalia and as craniofacial morphogenesis.

No abstract

No abstract

Migraine is characterised by debilitating pain, which affects the quality of life in affected patients in both the western and the eastern worlds. The purpose of this article is to give a detailed outline of the pathophysiology of migraine pain, which is one of the most confounding pathologies among pain disorders in clinical conditions. We critically evaluate the scientific basis of various theories concerning migraine pathophysiology, and draw insights from brain imaging approaches that have unraveled the prevalence of cortical spreading depression (CSD) in migraine. The findings supporting the role of CSD as a physiological substrate in clinical pain are discussed. We also give an exhaustive overview of brain imaging approaches that have been employed to solve the genesis of migraine pain, and its possible links to the brainstem, the neocortex, genetic endophenotypes, and pathogenetic factors (such as dopaminergic hypersensitivity). Furthermore, a roadmap is proposed to provide a better understanding of pain pathophysiology in migraine, to enable the development of strategies using leads from brain imaging studies for the identification of early biomarkers, efficient prognosis, and treatment planning, which eventually may help in alleviating some of the devastating impact of pain morbidity in patients afflicted with migraine.

No abstract