ABSTRACT
Neurodegenerative diseases affect a considerable percentage of the elderly population. New therapeutic approaches are warranted, aiming to at least delay and possibly reverse disease progression. Strategies to elaborate such approaches require knowledge of specific immune system involvement in disease pathogenesis. In this review, innate and adaptive immunological aspects of neurodegenerative disorders, in particular Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis (ALS), are discussed. Initiating disease factors, as well as common mechanistic pathways, are detailed and potential immunological therapeutic targets are identified.
Subject(s)
Adaptive Immunity/physiology , Immunity, Innate/physiology , Neurodegenerative Diseases/immunology , Animals , Humans , Neurodegenerative Diseases/metabolismABSTRACT
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive motor neuron death, leading to muscle atrophy, paralysis, and death usually within 3 to 5 years after diagnosis. Most cases are sporadic, with still undefined etiopathogenesis. Both the innate and adaptive immune systems are involved in ALS, with special participation of T lymphocytes and microglia. Inflammation plays a dual role in the disease, protective and T regulatory cell rich in the early stages and deleterious as disease progresses. Attempts to modulate immune/inflammatory system response are reported in the literature, and while beneficial effects are achieved in ALS animal models, results of most clinical trials have been disappointing. The impaired blood-brain barrier is an important feature in the pathogenesis of ALS and likely affects the immune system response. The present review describes the role of the immune system in ALS pathogenesis and the tight coupling of immunity and central nervous system barrier function.
ABSTRACT
Cerebrovascular diseases are a major cause of death and long-term disability in developed countries. Tissue plasmin activator (tPA) is the only approved therapy for ischemic stroke, strongly limited by the short therapeutic window and hemorrhagic complications, therefore excluding most patients from its benefits. The rescue of the penumbra area of the ischemic infarct is decisive for functional recovery after stroke. Inflammation is a key feature in the penumbra area and it plays a dual role, improving injury in early phases but impairing neural survival at later stages. Stem cells can be opportunely used to modulate inflammation, abrogate cell death and, therefore, preserve neural function. We here discuss the possible role of stem cells derived from menstrual blood as restorative treatment for stroke. We highlight the availability, proliferative capacity, pluripotentiality and angiogenic features of these cells and explore their present and future experimental and clinical applications.