The role and therapeutic potential of monocytic cells in Alzheimer's disease

Abstract

Alzheimer's disease (AD) is a dementing neurodegenerative disorder without a cure. The abnormal parenchymal accumulation of b-amyloid (Ab) is associated with inflammatory reactions involving microglia and astrocytes. Increased levels of Ab and Ab deposition in the brain are thought to cause neuronal dysfunction and underlie dementia. Microglia, the brain resident cells of monocytic origin, have a potential ability to phagocytose Ab but they also react to Ab by increased production of proinflammatory toxic agents. Microglia originate from hemangioblastic mesoderm during early embryonic stages and from bone marrow (BM)-derived monocytic cells that home the brain throughout the neonatal stage of development. Recent studies indicate that BM or blood-derived monocytes are recruited to the diseased AD brain, associate with the Ab depositions, and are more efficient phagocytes of Ab compared with resident microglia. The clearance of Ab deposition by these cells has been recently under intensive investigation and can occur through several different mechanisms. Importantly, peripheral monocytic cells of patients with AD appear to be deficient in clearing Ab. This review will summarize the findings on the role of blood-derived cells in AD and discuss their therapeutic potential for treating patients suffering from this devastating disease. V

Juzen-Taiho-To, an Herbal Medicine, Promotes the Differentiation of Transplanted Bone Marrow Cells into Microglia in the Mouse Brain Injected with Fibrillar Amyloid <i>β</i>

“…Many studies confirmed that BMSC could enter the CNS, and differentiate into functional microglia (Priller et al 2001a, b;Vallieres and Sawchenko 2003;Simard and Rivest 2004;Massengale et al 2005;Malm et al 2010). Although some researchers thought that BMSC could enter the normal brain with intact BBB (Vallieres and Sawchenko 2003;Simard and Rivest 2004), they were more easily attracted to the regions involved in neurodegenerative diseases or other neurological disorders (Priller et al 2001a(Priller et al , b, 2006Vallieres and Sawchenko 2003;Villeneuve et al 2005;Simard et al 2006).…”

“…In recent years, microglia, which are derived from bone marrow stem cells (BMSC), have become a hot topic. Many studies gave evidence that BMSC could penetrate through the bloodbrain barrier (BBB) into the central nervous system (CNS), and differentiate into functional microglia (Hess et al 2004;Simard and Rivest 2004;Malm et al 2005Malm et al , 2010Massengale et al 2005). However, it remains controversial whether or not BMSC could enter the normal brain.…”

Biogerontology in Finland

“…In the Department of Neurobiology (A. I. Virtanen Institute for Molecular Sciences, Biocenter Kuopio) there is research on the impact of aging on brain plasticity and on the factors that contribute to neurodegeneration and brain injury, especially age-related diseases affecting the immune system. The group uses both cell and animal models as well primary human cells to reveal the key molecular mechanisms (Kanninen et al 2009;Malm et al 2010). There is intensive collaboration with numerous European, North American and Japanese academic research groups and with pharmaceutical industry.…”

Immunopathogenetic Aspects of Ischemic Stroke

“…В отличие от клеток микроглии, рекрутируе-мые с периферии макрофаги более резистентны к повреждающему действию ишемии и активно вовлекаются в процессы элиминации клеточно-го дебриса на протяжении первых 7 дней после инсульта [100]. Учитывая более высокую фагоци-тарную активность рекрутируемых макрофагов по сравнению с клетками микроглии [74], эти клетки могут играть более значимую роль в про-цессах нейрональной пластичности и ремодели-рования при церебральной ишемии.…”