Alzheimer's disease is a severe, highly disabling neurodegenerative disease, clinically characterized by a progressive decline in cognitive functions, and is the most common form of dementia in the elderly. For de...Alzheimer's disease is a severe, highly disabling neurodegenerative disease, clinically characterized by a progressive decline in cognitive functions, and is the most common form of dementia in the elderly. For decades, the search for disease-modifying therapies has focused on the two main Alzheimer's disease histopathological hallmarks, seeking to prevent, mitigate, or clear the formation of extracellular aggregates of β-amyloid peptide and intracellular neurofibrillary tangles of tau protein, although without clinical success. Mesenchymal stem cell-based therapy has emerged as a promising alternative for the treatment of Alzheimer's disease, especially because it also targets other crucial players in the pathogenesis of the disease, such as neuroinflammation, synaptic dysfunction/loss, oxidative stress, and impaired neurogenesis. Herein, we review current knowledge of the therapeutic potential of mesenchymal stem cells and their extracellular vesicles for Alzheimer's disease, discussing the most recent findings in both preclinical and clinical trials as well as how advanced technologies have helped to overcome some limitations and contributed to stimulate the development of more effective treatments.展开更多
Gangliosides,sialic acid-containing sphingolipids,are major constituents of neuronal membranes.According to the number of sialic acids and the structure of the oligosaccharide chain,gangliosides can be classified as s...Gangliosides,sialic acid-containing sphingolipids,are major constituents of neuronal membranes.According to the number of sialic acids and the structure of the oligosaccharide chain,gangliosides can be classified as simple or complex and grouped in different ganglio-series.Hundreds of gangliosides have been identified in vertebrate cells,with different expression patterns during development and related to several physiological processes,especially in the nervous system.While GD3 and its O-acetylated form,9acGD3,are highly expressed in early developmental stages,GM1,GD1a,GD1b,and GT1b are the most abundant ganglioside species in the mature nervous system.Mutations in enzymes involved in ganglioside metabolism can lead to the accumulation of specific species,a condition termed gangliosidosis and usually marked by severe neurological impairment.Changes in ganglioside levels have also been described in several neurodegenerative diseases,such as Alzheimer’s and Parkinson’s.In this review,we summarized recent information about the roles of GD3,9acGD3,GM1,GD1a,GD1b,GT1b,and other ganglioside species in nervous system development and regeneration,as well as clinical trials evaluating possible therapeutic applications of these molecules.展开更多
Amyotrophic lateral sclerosis（ALS） is a fatal neurodegenerative disease that causes progressive muscular atrophy and death within 3–5 years after its onset.Despite the significant advances in knowledge of ALS patho...Amyotrophic lateral sclerosis（ALS） is a fatal neurodegenerative disease that causes progressive muscular atrophy and death within 3–5 years after its onset.Despite the significant advances in knowledge of ALS pathology,no effective treatment is available.Therefore,it is imperative to search for new alternatives to treat ALS.Cell therapy,especially using bone-marrow cells,has showed to be very useful to protect the neural tissue in different brain disease or traumatic lesions.In ALS,most published results show beneficial effects of the use bone marrow cells,especially mesenchymal stromal cells.However,until now,the best outcome extends animal＇s lifespan by only a few weeks.It is essential to continue the search for a really effective therapy,testing different cells,routes and time-windows of administration.Studying the mechanisms that initiate and spread the degenerative process is also important to find out an effective therapy.Therefore,we discussed here some progresses that have been made using bone-marrow cell therapy as a therapeutic tool for ALS.展开更多
基金supported by gran ts and fellowships from the Deportomento de Ciência e Tecnologia (DECIT-MS) do Ministério da SaúdeConselho Nacionol de Desenvolvimento Científico e Tecnológico (CNPq)+2 种基金Instituto Nacional de Ciência e Tecnologia em Medicina RegenerotivaFundacao de AmporoàPesquisa do Estado do Rio de Janeiro(FAPERJ)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)(all to RMO)。
文摘Alzheimer's disease is a severe, highly disabling neurodegenerative disease, clinically characterized by a progressive decline in cognitive functions, and is the most common form of dementia in the elderly. For decades, the search for disease-modifying therapies has focused on the two main Alzheimer's disease histopathological hallmarks, seeking to prevent, mitigate, or clear the formation of extracellular aggregates of β-amyloid peptide and intracellular neurofibrillary tangles of tau protein, although without clinical success. Mesenchymal stem cell-based therapy has emerged as a promising alternative for the treatment of Alzheimer's disease, especially because it also targets other crucial players in the pathogenesis of the disease, such as neuroinflammation, synaptic dysfunction/loss, oxidative stress, and impaired neurogenesis. Herein, we review current knowledge of the therapeutic potential of mesenchymal stem cells and their extracellular vesicles for Alzheimer's disease, discussing the most recent findings in both preclinical and clinical trials as well as how advanced technologies have helped to overcome some limitations and contributed to stimulate the development of more effective treatments.
基金supported by grants and fellowships from the Departamento de Ciência e Tecnologia(DECIT/MS)do Ministério da Saúde,Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)Instituto Nacional de Ciência e Tecnologia em Medicina Regenerativa,Fundação de AmparoàPesquisa do Estado do Rio de Janeiro(FAPERJ)(to RMO).
文摘Gangliosides,sialic acid-containing sphingolipids,are major constituents of neuronal membranes.According to the number of sialic acids and the structure of the oligosaccharide chain,gangliosides can be classified as simple or complex and grouped in different ganglio-series.Hundreds of gangliosides have been identified in vertebrate cells,with different expression patterns during development and related to several physiological processes,especially in the nervous system.While GD3 and its O-acetylated form,9acGD3,are highly expressed in early developmental stages,GM1,GD1a,GD1b,and GT1b are the most abundant ganglioside species in the mature nervous system.Mutations in enzymes involved in ganglioside metabolism can lead to the accumulation of specific species,a condition termed gangliosidosis and usually marked by severe neurological impairment.Changes in ganglioside levels have also been described in several neurodegenerative diseases,such as Alzheimer’s and Parkinson’s.In this review,we summarized recent information about the roles of GD3,9acGD3,GM1,GD1a,GD1b,GT1b,and other ganglioside species in nervous system development and regeneration,as well as clinical trials evaluating possible therapeutic applications of these molecules.
基金supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico(www.cnpq.br)Coordenacao de Aperfeicoamento de Pessoal de Nível Superior(www.capes.gov.br)Fundacao Carlos Chagas Filho de AmparoàPesquisa do Estado do Rio de Janeiro(www.faperj.br)
文摘Amyotrophic lateral sclerosis（ALS） is a fatal neurodegenerative disease that causes progressive muscular atrophy and death within 3–5 years after its onset.Despite the significant advances in knowledge of ALS pathology,no effective treatment is available.Therefore,it is imperative to search for new alternatives to treat ALS.Cell therapy,especially using bone-marrow cells,has showed to be very useful to protect the neural tissue in different brain disease or traumatic lesions.In ALS,most published results show beneficial effects of the use bone marrow cells,especially mesenchymal stromal cells.However,until now,the best outcome extends animal＇s lifespan by only a few weeks.It is essential to continue the search for a really effective therapy,testing different cells,routes and time-windows of administration.Studying the mechanisms that initiate and spread the degenerative process is also important to find out an effective therapy.Therefore,we discussed here some progresses that have been made using bone-marrow cell therapy as a therapeutic tool for ALS.
