Ricardo Maccioni

University of Chile · Departamento de Neurología y Neurocirugía

Aging constitutes progressive physiological changes in an organism. These changes alter the normal biological functions, such as the ability to manage metabolic stress, and eventually lead to cellular senescence. The process itself is characterized by nine hallmarks: genomic instability, telomere attrition, epigenetic alterations, loss of proteosta...

Background Alzheimer’s disease is the most prevalent cause of dementia in the elderly. Neuronal death and synaptic dysfunctions are considered the main hallmarks of this disease. The latter could be directly associated to an impaired metabolism. In particular, glucose metabolism impairment has demonstrated to be a key regulatory element in the onse...

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disease characterized by progressive cognitive impairment, apathy, and neuropsychiatric disorders. Two main pathological hallmarks have been described: neurofibrillary tangles, consisting of tau oligomers (hyperphosphorylated tau) and Aβ plaques. The influence of protein kinases and pho...

Developmental signaling pathways such as Wnt/β-catenin, Notch and Sonic hedgehog play a central role in nearly all the stages of neuronal development. The term ‘embryonic’ might appear as a misnomer to several people because these pathways are functional during the early stages of embryonic development and adulthood, albeit to a certain degree. The...

Background: Clinically-evaluated nutraceuticals are candidates for Alzheimer's disease (AD) prevention and treatment. Phase I studies showed biological safety of the nutraceutical BrainUp-10®, while a pilot trial demonstrated efficacy for treatment. Cell studies demonstrated neuroprotection. BrainUp-10® blocks tau self-assembly. Apathy is the most...

One of the major puzzles in medical research and public health systems worldwide is Alzheimer’s disease (AD), reaching nowadays a prevalence near 50 million people. This is a multifactorial brain disorder characterized by progressive cognitive impairment, apathy, and mood and neuropsychiatric disorders. The main risk of AD is aging; a normal biolog...

One of the major challenges of medical sciences has been finding a reliable compound for the pharmacological treatment of Alzheimer’s disease (AD). As most of the drugs directed to a variety of targets have failed in finding a medical solution, natural products from Ayurvedic medicine or nutraceutical compounds emerge as a viable preventive therape...

Several hypotheses have been postulated to explain how Alzheimer's disease is triggered, but none of them provide a unified view of its pathogenesis. The dominant hypothesis based on build-ups of the amyloid-β peptide has been around for longer than three decades; however, up to today, numerous clinical trials based on the amyloid postulates have b...

Background: Alzheimer's disease (AD) is a multifactorial disease, that involves neuroinflammatory processes in which microglial cells respond to "damage signals". The latter includes oligomeric tau, iron, oxidative free radicals, and other molecules that promotes neuroinflammation in the brain, promoting neuronal death and cognitive impairment. Si...

Neurodegenerative diseases share the fact that they derive from altered proteins that undergo an unfolding process followed by formation of β-structures and a pathological tendency to self-aggregate in neuronal cells. This is a characteristic of tau protein in Alzheimer’s disease and several tauopathies associated with tau unfolding, α-synuclein in...

Alzheimer´s disease (AD) and related dementias are impacting the aging population throughout the world, at an alarming rate. World Alzheimer´s Report indicates a prevalence of 46.8 million affected with AD worldwide. As population ages, this number is projected to triple by 2050 unless effective interventions can be developed and implemented. Urgen...

The cyclin-dependent kinase 5 (CDK5) is known as an exceptional component of the CDK family, due to its characteristic regulatory pathways and its atypical roles in comparison to the classical cyclins. Despite its functional uniqueness, CDK5 shares a great part of its structural similarity with other members of the cyclin-dependent kinase family. A...

The establishment of a molecular biomarker for early detection of Alzheimer's disease (AD) is critical for diagnosis and follow up of patients, and as a quantitative parameter in the evaluation of potential new drugs to control AD. A list of blood biomarkers has been reported but none has been validated for the Alzheimer's clinic. The changes in hy...

The present invention relates to pyridine methyl sulfinyl benzoxazole compounds and pyridine methyl sulfinyl benzothiazole compounds, tagged radioactively or fluorescently, and compositions thereof, as specific biomarkers for the diagnosis of neurodegenerative diseases and pathologies involving tau protein, such as Alzheimer’s and other dementias....

Evidence-based Nutraceutical Compounds (EBNC), containing bioactive principles of demonstrated efficacy and health security are opening solutions for a modern preventive medicine, and as potential solutions for many chronic diseases of the human beings. EBNC contain bioactive components of the human diet that can be used for the prevention or treat...

Background Alzheimer’s Disease (AD) is a severe neurodegenerative disorder that includes the occurrence of behavioral disorders as well as memory and cognitive impairment as major symptoms. AD affects around 12% of the aged population in the world. Considerable research efforts have pointed to the role of innate immunity as the main culprit in the...

Alzheimer's disease (AD) is the most frequent type of dementia in the elderly, severely affecting functional and executive skills of subjects suffering from this disease. Moreover, the distress of caregivers as well as the social implications constitute a critical issue for families. Furthermore, cognitive impairment, along with behavioral disorder...

Progressive neurodegenerative pathologies in aged populations are an issue of major concern worldwide. The microtubule-associated protein tau is able to self-aggregate to form abnormal supramolecular structures that include small oligomers up to complex polymers. Tauopathies correspond to a group of diseases that share tau pathology as a common eti...

Alzheimer’s disease (AD) is a neurodegenerative disease, the most common cause of dementia in senile population. According to the World Health Organization, AD represents around 12% of people over 65 worldwide. Due to its etiological agents, neurofibrillary tangles (NFT) and amyloid plaques (AP), several attempts to explain the genesis and progress...

Alzheimer's disease (AD) is a neurodegenerative disease characterized by a progressive cognitive impairment of patients, affecting around 12% of people older than 65 years old. WHO estimated that over 48.6 million all over the world suffer this disease. On the basis of cumulative results on our research, we have postulated the neuroimmunomodulation...

Cumulative evidence shows that innate immunity participates in the pathogenesis of Alzheimer´s disease. This implies that activation of microglia by the so called “damaged signals” triggers a cascade of pathological molecular events thus leading to hyperphosphorylation and oligomerization of the tau protein in the brain, which is associated with co...

Background: Intracellular neurofibrillary tangles are part of the core pathology of Alzheimer's disease (AD), which are mainly composed of hyperphosphorylated tau protein. Objectives: The purpose of this study is to determine whether high molecular weight (HMW) or low molecular weight (LMW) tau protein levels, as well as the ratio HMW/LMW, prese...

Pathophysiological processes of neurodegenerative diseases are not clearly defined. However, an important body of evidence points toward the role of various inflammatory processes. The microglial cell is the main representative of the immune system in the central nervous system (CNS). This cell type can sense foreign or harmful pathogens and trigge...

Many biomarkers are currently being searched in neurodegenerative diseases like Alzheimer's disease and Parkinson's disease. These diseases share some common pathophysiological mechanisms and the presence of protein aggregates. Measurements of those proteins-like tau, amyloid-beta peptide and α-synuclein-, as well other mediators of neurodegenerati...

The present invention is directed to a method for early, non-invasive, rapid, efficient, reliable and accurate diagnose of Alzheimer's disease. The present invention particularly addresses obtaining blood samples, and stabilizing platelets from healthy persons and patients with probable cognitive impairment and/or Alzheimer's disease; extracting pr...

Microglial cells play a major role in the innate immunity of the central nervous system. Alterations in the normal cross-talks between microglia and brain neuronal cells may lead to serious disturbances and neurodegenerative diseases. We have postulated that neuroinflammatory processes are a critical factor triggering the pathological cascade leadi...

Microglial cells play a major role in the innate immunity of the central nervous system. Alterations in the normal cross-talks between microglia and brain neuronal cells may lead to serious disturbances and neurodegenerative diseases. We have postulated that neuroinflammatory processes are a critical factor triggering the pathological cascade leadi...

Ketoacidosis is a potentially life-threatening complication in patients with type 1 diabetes mellitus (T1DM), particularly children. If diabetic ketoacidosis (DKA) is diagnosed late, the child risks cerebral edema, permanent neurological damage or even death. There have been only few studies of DKA in Italy.

Alzheimer's disease is a growing health problem worldwide. The pharmaceutical industry has not recently developed any new drugs that have had a significant impact on the natural history of the disease, so considerable attention has been given to nutraceuticals and nutritional bioactive compounds that can be obtained directly from diet or supplement...

Negli ultimi anni è stata posta una crescente attenzione sulla remissione nella schizofrenia, grazie all’introduzione di una serie di criteri stabiliti dal “Gruppo di Lavoro sulla Remissione nella Schizofrenia” (Andreasen et al, 2005). Allo stesso tempo si è sollevato un grande dibattito nella comunità scientifica riguardo alla validità di tali cri...

Alzheimer disease (AD) is the most common cause of dementia in people over 60 years old. The molecular and cellular alterations that trigger this disease are still diffuse, one of the reasons for the delay in finding an effective treatment. In the search for new targets to search for novel therapeutic avenues, clinical studies in patients who used...

A cumulative number of approaches have been carried out to elucidate the pathogenesis of Alzheimer's disease (AD). Tangles formation has been identified as a major event involved in the neurodegenerative process, due to the conversion of either soluble peptides or oligomers into insoluble filaments. Most of recent studies share in common the observ...

Neuroinflammation is a process related to the onset of several neurodegenerative disorders, including Alzheimer's disease (AD). Increasing sets of evidence support the major role of deregulation of the interaction patterns between glial cells and neurons in the pathway toward neuronal degeneration, a process we are calling neuroimmunomodulation in...

Alzheimer's disease (AD) diagnosis still depends on the triad of clinical, imaging and neuropsychological testing. The development of accurate, easy to use and inexpensive biological markers for AD is a long-standing aspiration for researchers and the medical community. Here we describe some of the recent advances in the field of biomarkers, both i...

Alzheimer's disease (AD) is a brain disorder displaying a prevalence and impact in constant expansion. This expansive and epidemic behavior is concerning medical and public opinion while focusing efforts on its prevention and treatment. One important strategy to prevent this brain impairment is based on dietary changes and nutritional supplements,...

Alzheimer disease (AD) is the most common neurodegenerative disorder involving amyloid-β and neurofibrillary tangles, composed by hyperphosphorylated tau protein. We investigate parietin 1 in the context of their action to prevent tau alterations in the etiopathogenesis of AD. Xanthoria ectaneoides and Arthopyrenia saxicola, two marine lichens, wer...

Platelets are major reservoirs of circulating amyloid-β and amyloid-β protein precursor (AβPP) and have been postulated as a reliable source for biological markers of Alzheimer's disease (AD). We have recently demonstrated that tau is also present in platelets, and that there are differences in the electrophoretic patterns of platelet tau forms in...

Shilajit is a natural substance found mainly in the Himalayas, formed for centuries by the gradual decomposition of certain plants by the action of microorganisms. It is a potent and very safe dietary supplement, restoring the energetic balance and potentially able to prevent several diseases. Recent investigations point to an interesting medical a...

The neurofibrillary tangles (NFTs) generated by self-aggregation of anomalous forms of tau represent a neuropathological hallmark of Alzheimer's disease (AD). These lesions begin to form long before the clinical manifestation of AD, and its severity is correlated with cognitive impairment in patients. We focused on the search for molecules that int...

The neuronal cytoskeleton regulates numerous processes that occur in normal homeostasis. Under pathological conditions such as those of Alzheimer's disease (AD), major alterations in cytoskeleton organization have been observed and changes in both microtubules and actin filaments have been reported. Many neurodegenerative consequences of AD are lin...

Alzheimer's disease is a neurodegenerative disorder involving extracellular plaques (amyloid-β) and intracellular tangles of tau protein. Recently, tangle formation has been identified as a major event involved in the neurodegenerative process, due to the conversion of either soluble peptides or oligomers into insoluble filaments. At present, the c...

The anomalous aggregation of proteins into pathological filaments is a common feature of a many human diseases, often related to aging. In this context, neurodegenerative pathologies such as Alzheimer's disease (AD) account for a major part of these protein misfolding diseases. AD is characterized by pathological aggregation of two proteins, tau an...

A major limitation in finding therapeutic solutions for Alzheimer's disease (AD) has been the lack of a reliable method for early diagnosis of this devastating disease. Besides the development of biomarkers in biological fluids of patients, the search for a pathology-specific neuroimaging tools is critical at the present stage in which almost 30 mi...

Pathological tau protein aggregates can be found in brain of patients with some of the neurodegenerative diseases collectively known as tauopathies, which include Alzheimer's disease (AD). Since tau post-translational modifications including phosphorylations, glycosylations, truncation and the subsequent aggregation in oligomers, paired helical fil...

Platelets are a major peripheral reservoir of the amyloid-β protein precursor, so they have been considered as a potential biological marker of Alzheimer's disease (AD). Here, it is demonstrated that tau protein is also present in platelets and that the levels of oligomeric species of this protein could serve as a novel and reliable biological mark...

Cow's milk protein allergy (CMPA) affects 2-7.5% of children; persistence in adulthood is uncommon since a tolerance develops in 51% of cases within 2 years and 80% within 3-4 years. CMPA is an immunological reaction to one or more milk proteins: α-lactalbumin, ß-lactoglobulin, casein, IgE or non-IgE associated, responsible of immediate or late ons...

Interleukin-3 (IL-3) regulates the proliferation, survival and differentiation of haematopoietic cells via interaction with specific cell-surface receptors. IL-3 is expressed in several non-hematopoietic cell types. Studies have demonstrated the presence of IL-3 in the central nervous system, however, its physiological role in these cells is poorly...

Platelets are a major peripheral reservoir of the amyloid-protein precursor, so they have been considered as a potential biological marker of Alzheimer's disease (AD). Here, it is demonstrated that tau protein is also present in platelets and that the levels of oligomeric species of this protein could serve as a novel and reliable biological marker...

Many hypotheses have been raised regarding the pathophysiology of Alzheimer's disease (AD). Because amyloid beta peptide (Abeta) deposition in senile plaques appears as a late, nonspecific event, recent evidence points to tau phosphorylation and aggregation as the final common pathway in this multifactorial disease. Current approaches that provide...

The progressive increase in life expectancy of the world population has fostered a major concern in order to fnd effective avenues for diagnosis of treatment of Alzheimés disease (AD). Even tough AD pathogenesis is still unclear, new advances have allowed to understand that exposure of individuals to a series of environmental risk factors, named to...

El constante aumento en la expectativa de vida en la población mundial ha incrementado la preocupación hacia la búsqueda de la comprensión de la Enfermedad de Alzheimer (EA), así como de su diagnóstico temprano y tratamiento. Actualmente la etiopatogenia que conduce al desarrollo de la EA es aún difusa, pero se ha llegado a comprender que la exposi...

Use of benzimidazole-derived compounds of formula (I) according to the following structure, wherein x is a heteroatom selected from N, S, O, P, SO, SO2 and SO3, preferably from N, S and SO3 and most preferably from N and SO3; n may be 0 or 1, R1 is a group selected from formula (II) and formual (III) and R2 is a group selected from H and formula (I...

Evidence has been cumulated on the role of microglia cells deregulation and alterations in their interaction patterns with brain neurons, in the pathway towards neurodegeneration in Alzheimer's disease (AD). After the failure of the amyloid hypothesis to explain AD pathogenesis, current hypotheses focus on tau self-polymerization into pathological...

We describe the interactions of two benzimidazole derivatives, astemizole (AST) and lansoprazole (LNS), with anomalous aggregates of tau protein (neurofibrillary tangles). Interestingly, these compounds, with important medical applications in the treatment of allergies and gastrointestinal disorders respectively, specifically bind to aggregated var...

Chitosan is a D-glucosamine polysaccharide derived from chitin that displays an antimicrobial activity against bacteria and fungi. Objective: to evaluate the antifungal effect of high molecular weight chitosan (HMWC) in clinical strains of Candida spp. Methodology: the susceptibility of forty strains of Candida spp. to HMWC was studied (16 C albica...

We describe the interactions of two benzimidazole derivatives, astemizole (AST) and lansoprazole (LNS), with anomalous aggregates of tau protein (neurofibrillary tangles). Interestingly, these compounds, with important medical applications in the treatment of allergies and gastrointestinal disorders respectively, specifically bind to aggregated var...

Several cytisine derivatives have been developed in the search for more selective drugs at nicotinic acetylcholine receptors (nAChR). Binding experiments in transfected cell lines showed that the iodination of cytisine in the position 3 of the pyridone ring increased potency at alpha7-nAChR and to a lesser extent at the alpha4beta2 subtypes, both o...