oa Editorial [The Multifactorial Nature of Alzheimer's Disease and Related Therapeutic Strategies (Executive Editors: Maria do Carmo Carreiras and Jose Marco-Contelles)]

Alzheimer's disease (AD) is a neurodegenerative, irreversible disorder clinically characterized by abnormal memory loss along with deterioration of other cognitive abilities as well as motor capacities. AD is a progressive and disabling disorder, which affects particularly the elderly population and is the fourth main cause of death among people over 65 years old in industrialized countries. The greatest risk factor for cognitive decline and AD in older adults is age itself. This disorder represents a considerable burden for patients, caregivers and society. However, therapeutic options for AD still remain extremely restrained. Present research on senile dementia and AD aims for a new generation of drugs which may represent a disease-modifying-treatment that will hinder or halt disease progression. This special issue of Current Pharmaceutical Design highlights some important aspects concerning the multifactorial nature of AD and the related proposed therapeutic strategies. The first article by Paula Agostinho and co-workers [1] elucidates the involvement of microglia and astrocytes in the onset and progress of neurodegenerative process in AD, and recommends therapeutic strategies directed at controlling the activation of microglia and astrocytes. The second article by Masahiro Kawahara [2] outlines the current understanding of AD pathology based on the hypothesis that disruption of calcium homeostasis through amyloid channels may be the molecular basis of Aβ neurotoxicity, and points out the development of preventive agents based on the amyloid channel hypothesis. The next article by Medina and Avila [3] reviews the role of Glycogen Synthase Kinase-3 (GSK-3) in a series of cellular processes involved in AD pathology, and proposes inhibition of GSK-3 to slow down progression of neurodegeneration in AD and other tauopathies. The article by Naoi and Maruyama [4] presents the molecular mechanisms behind neuroprotection by monoamine oxidase inhibitors and discusses the possible development of new drugs to prevent, delay and restore neuronal cell death in Alzheimer's and Parkinson's diseases. The next article by Munoz-Torrero, Javier Luque and colleagues [5] specifies the structural determinants which mediate the interaction of dual binding site AChE inhibitors, a new class of anti-Alzheimer agents with potential to positively modify the course of the disease. The sixth article by Martinez-Murillo and collaborators [6] elucidates the implication of nitric oxide in the progression of the disease and advances the use of subtype selective nitric oxide synthase inhibitors (NOS) to target NOS isoforms implicated in damage to brain cells in AD. The final article by Rui Castro, Maria Santos and colleagues [7] focuses on molecular mechanisms of apoptosis in AD and highlights the potential use of small molecule modulators to treat neurodegenerative disorders. We would like to thank all the contributing authors for their time and efforts in the compilation of this issue. Our special thanks to all the scientists who aided in the peer-review process in a timely manner. We also extend our appreciation to Dr. William A. Banks, editor-in-chief of Current Pharmaceutical Design, for granting us this opportunity, and to the editorial and publication team of Bentham Science for their cooperation and efforts in getting this special issue ready to the readers.....