SPECIAL FOCUS y The Current and Future Use of Alzheimer’s Disease Therapeutics
Review
Expert Review of Neurotherapeutics Downloaded from informahealthcare.com by Washington University Library on 12/30/14 For personal use only.
Nutraceuticals and amyloid neurodegenerative diseases: a focus on natural phenols Expert Rev. Neurother. Early online, 1–12 (2014)
Stefania Rigacci1 and Massimo Stefani*1,2 1 Department of Experimental and Clinical Biomedical Sciences ‘Mario Serio,’ University of Florence, Viale Morgagni, 50, 50134 Florence, Italy 2 Research Centre on the Molecular Basis of Neurodegeneration, Viale Morgagni, 50, 50134 Florence, Italy *Author for correspondence [email protected]
A common molecular feature of amyloid neurodegenerative diseases is the unfolding/ misfolding of specific proteins/peptides which consequently become prone to aggregate into toxic assemblies and deposits that are the key histopathological trait of these pathologies. Apart from the rare early-onset familiar forms, these neurodegenerative diseases are age-associated disorders whose symptoms appear in aged people after long incubation periods. This makes the therapeutic approach particularly compelling and boosts the search for both early diagnostic tools and preventive approaches. In this last respect, natural compounds commonly present in foods and beverages are considered promising molecules, at least on the bench side. The so-called ‘nutraceutical approach’ suggests life-long healthy diets, particularly focusing on food molecules that are candidates to enter clinical trials as such or following a targeted molecular engineering. Natural phenols abundant in ‘healthy’ foods such as extra virgin olive oil, red wine, green tea, red berries and spices, appear particularly promising. KEYWORDS: Alzheimer’s disease • Asian diet • curcumin • EGCG • Ginkgo biloba • Mediterranean diet • nanoparticles • oleocanthal • oleuropein aglycone • resveratrol
Healthy eating & aging
Ensuring a long and healthy life has always been a main goal of medical research and, certainly, the great progresses of modern medicine have highly contributed to combating several severe pathologies, such as cancer, that only a few decades ago were largely fatal. As a result, the life expectancy has considerably increased in western countries; however, this achievement has been paralleled by a greater incidence of lifestyle-associated diseases such as cardiovascular disease and Type 2 diabetes as well as of various forms of age-associated cognitive decline. The latter conditions develop during a very long period of time before the appearance of symptoms with the exception of genetically determined familial forms and span from the relatively benign mild cognitive impairment (MCI) to the much more severe forms of dementia, notably Alzheimer’s disease (AD). In most cases, neurodegenerative diseases are accompanied by shared histopathological signs consisting of intracellular or extracellular deposits whose main component is a fibrillar
informahealthcare.com
10.1586/14737175.2015.986101
proteinaceous material arising from the polymerization of one out of a number of peptides/ proteins following misfolding and subsequent aggregation. These polymeric fibrils display shared structural features commonly referred to as the ‘amyloid fold’ [1] because of their strict similarity to the fibrils found in non-nervous tissues whose deposits characterize ‘classical’ amyloid diseases, including primary systemic amyloidosis, secondary systemic amyloidosis, senile systemic amyloidosis and Type 2 diabetes (TABLE 1). The ‘amyloid hypothesis’ of AD (and possibly other neurodegenerative pathologies with amyloid deposits) traces back to the presence of extracellular amyloid aggregates of the Ab peptide the onset of cell sufferance and synaptic failure whose progressive worsening results in increasingly severe cognitive impairment [2]. Even though the amyloid hypothesis is questioned by some authors and several variants to it have been proposed, at present, it is strongly believed that a valuable approach to avoid or to delay the onset of neurodegenerative diseases with amyloid deposits is prevention; the
2014 Informa UK Ltd
ISSN 1473-7175
1
Review
Rigacci & Stefani
Expert Review of Neurotherapeutics Downloaded from informahealthcare.com by Washington University Library on 12/30/14 For personal use only.
Table 1. The recognized amyloid diseases.†
different world areas (the eastern Afromontane and Albertine Rift region of Clinical syndrome Fibril component Ethiopia, the Maya Mountains region of Alzheimer’ s disease Ab peptides Belize, the Western Ghats region of India and the Appalachian Mountains region of Spongiform encephalopathies Prion (whole or fragment) the USA). The results revealed that, Parkinson’ s disease a-synuclein (wt or mutant) besides fundamental personal and social Familial Danish dementia ADan (fragment of Bri-277) habits (positive outlook, engagement in family and social group, physical and Familial British dementia ABri (fragment of Bri-277) mental exercise, traditional healing practiFronto-temporal dementia Tau (wt or mutant) ces, strong spirituality), a calorie-sparse, nutrient-dense, plant-based diet is a comHereditary cerebral amyloid Cystatin C (truncated) angiopathy mon characteristic [3]. The effectiveness of a healthy diet and Amyotrophic lateral sclerosis Superoxide dismutase lifestyle in improving cognitive functions Dentatorubro-pallido Luysian Atrophin 1 was recently confirmed by a 2-year atrophy intervention (The Finnish Geriatric InterHuntington disease Huntingtin (whole or poly(Q) fragment) vention Study to Prevent Cognitive Impairment and Disability [4]) with a comCerebellar ataxia Ataxins (whole or poly(Q) fragment) bination of nutritional guidance (a recomKennedy disease Androgen receptor (whole or poly(Q) fragment) mended diet rich in fruits and vegetables, whole grains, low fat, sucrose intake
Review
Expert Review of Neurotherapeutics Downloaded from informahealthcare.com by Washington University Library on 12/30/14 For personal use only.
Nutraceuticals and amyloid neurodegenerative diseases: a focus on natural phenols Expert Rev. Neurother. Early online, 1–12 (2014)
Stefania Rigacci1 and Massimo Stefani*1,2 1 Department of Experimental and Clinical Biomedical Sciences ‘Mario Serio,’ University of Florence, Viale Morgagni, 50, 50134 Florence, Italy 2 Research Centre on the Molecular Basis of Neurodegeneration, Viale Morgagni, 50, 50134 Florence, Italy *Author for correspondence [email protected]
A common molecular feature of amyloid neurodegenerative diseases is the unfolding/ misfolding of specific proteins/peptides which consequently become prone to aggregate into toxic assemblies and deposits that are the key histopathological trait of these pathologies. Apart from the rare early-onset familiar forms, these neurodegenerative diseases are age-associated disorders whose symptoms appear in aged people after long incubation periods. This makes the therapeutic approach particularly compelling and boosts the search for both early diagnostic tools and preventive approaches. In this last respect, natural compounds commonly present in foods and beverages are considered promising molecules, at least on the bench side. The so-called ‘nutraceutical approach’ suggests life-long healthy diets, particularly focusing on food molecules that are candidates to enter clinical trials as such or following a targeted molecular engineering. Natural phenols abundant in ‘healthy’ foods such as extra virgin olive oil, red wine, green tea, red berries and spices, appear particularly promising. KEYWORDS: Alzheimer’s disease • Asian diet • curcumin • EGCG • Ginkgo biloba • Mediterranean diet • nanoparticles • oleocanthal • oleuropein aglycone • resveratrol
Healthy eating & aging
Ensuring a long and healthy life has always been a main goal of medical research and, certainly, the great progresses of modern medicine have highly contributed to combating several severe pathologies, such as cancer, that only a few decades ago were largely fatal. As a result, the life expectancy has considerably increased in western countries; however, this achievement has been paralleled by a greater incidence of lifestyle-associated diseases such as cardiovascular disease and Type 2 diabetes as well as of various forms of age-associated cognitive decline. The latter conditions develop during a very long period of time before the appearance of symptoms with the exception of genetically determined familial forms and span from the relatively benign mild cognitive impairment (MCI) to the much more severe forms of dementia, notably Alzheimer’s disease (AD). In most cases, neurodegenerative diseases are accompanied by shared histopathological signs consisting of intracellular or extracellular deposits whose main component is a fibrillar
informahealthcare.com
10.1586/14737175.2015.986101
proteinaceous material arising from the polymerization of one out of a number of peptides/ proteins following misfolding and subsequent aggregation. These polymeric fibrils display shared structural features commonly referred to as the ‘amyloid fold’ [1] because of their strict similarity to the fibrils found in non-nervous tissues whose deposits characterize ‘classical’ amyloid diseases, including primary systemic amyloidosis, secondary systemic amyloidosis, senile systemic amyloidosis and Type 2 diabetes (TABLE 1). The ‘amyloid hypothesis’ of AD (and possibly other neurodegenerative pathologies with amyloid deposits) traces back to the presence of extracellular amyloid aggregates of the Ab peptide the onset of cell sufferance and synaptic failure whose progressive worsening results in increasingly severe cognitive impairment [2]. Even though the amyloid hypothesis is questioned by some authors and several variants to it have been proposed, at present, it is strongly believed that a valuable approach to avoid or to delay the onset of neurodegenerative diseases with amyloid deposits is prevention; the
2014 Informa UK Ltd
ISSN 1473-7175
1
Review
Rigacci & Stefani
Expert Review of Neurotherapeutics Downloaded from informahealthcare.com by Washington University Library on 12/30/14 For personal use only.
Table 1. The recognized amyloid diseases.†
different world areas (the eastern Afromontane and Albertine Rift region of Clinical syndrome Fibril component Ethiopia, the Maya Mountains region of Alzheimer’ s disease Ab peptides Belize, the Western Ghats region of India and the Appalachian Mountains region of Spongiform encephalopathies Prion (whole or fragment) the USA). The results revealed that, Parkinson’ s disease a-synuclein (wt or mutant) besides fundamental personal and social Familial Danish dementia ADan (fragment of Bri-277) habits (positive outlook, engagement in family and social group, physical and Familial British dementia ABri (fragment of Bri-277) mental exercise, traditional healing practiFronto-temporal dementia Tau (wt or mutant) ces, strong spirituality), a calorie-sparse, nutrient-dense, plant-based diet is a comHereditary cerebral amyloid Cystatin C (truncated) angiopathy mon characteristic [3]. The effectiveness of a healthy diet and Amyotrophic lateral sclerosis Superoxide dismutase lifestyle in improving cognitive functions Dentatorubro-pallido Luysian Atrophin 1 was recently confirmed by a 2-year atrophy intervention (The Finnish Geriatric InterHuntington disease Huntingtin (whole or poly(Q) fragment) vention Study to Prevent Cognitive Impairment and Disability [4]) with a comCerebellar ataxia Ataxins (whole or poly(Q) fragment) bination of nutritional guidance (a recomKennedy disease Androgen receptor (whole or poly(Q) fragment) mended diet rich in fruits and vegetables, whole grains, low fat, sucrose intake
