Neurodegenerative diseases are complex disorders with several pathoetiological pathways leading to cell death. Rationally designed multi-targeted agents, or "multi-targeted designed drugs" (MTDD) show significant promise in preclinical studies as…
We have previously shown that nicotine, the addictive component of tobacco products, alters the blood-brain barrier (BBB) Na+, K+, 2Cl(-) cotransporter (NKCC) during in vitro hypoxia-aglycemia exposure. Attenuation of abluminal NKCC suggests that…
Inadequacies of the current pharmacotherapies to treat Parkinson's disease (PD) have prompted efforts to identify novel drug targets. The adenosine A(2A) receptor is one such target. Antagonists of this receptor (A(2A) antagonists) are considered…
Exposure to the industrial solvent, styrene, induces locomotor and cognitive dysfunction in rats, and parkinsonian-like manifestations in man. The antipsychotic, haloperidol (HP), well known to induce striatal toxicity in man and animals, and styrene…
The multiple disease etiologies that lead to neuropsychiatric disorders, such as Parkinson's and Alzheimer's disease, amyotrophic lateral sclerosis, Huntington disease, schizophrenia, depressive illness and stroke, offer significant challenges to…
This chapter discusses the rationale for developing multimodal or multifunctional drugs (also called designed multiple ligands or DMLs) aimed at disease-modifying treatment strategies for the most common neurodegenerative diseases Alzheimer's and…
Parkinson's disease (PD) is a severe neurodegenerative disorder, with no available drugs able to prevent the neuronal cell loss characteristic in brains of patients suffering from PD. Due to the complex cascade of molecular events involved in the…
Polycyclic hydrocarbon compounds, also known as "cage compounds", are of interest in drug discovery due to their versatility as scaffolds. Derivatives of both pentacycloundecane-dione and triquinane-dione have been the focus of numerous…
Polycyclic cage scaffolds have been successfully used in the development of numerous lead compounds demonstrating activity in the central nervous system (CNS). Several neurodegenerative diseases, such as Alzheimers disease, Parkinsons disease,…
Metal homeostasis is increasingly being evaluated as a therapeutic target in stroke and neurodegenerative diseases. Metal dysregulation has been shown to lead to protein aggregation, plaque formation and neuronal death. In 2007, we first reported…
Development and progression of neurodegenerative disorders have, amongst other potential causes, been attributed to a disruption of iron regulatory mechanisms and iron accumulation. Excess extracellular iron may enter cells via nontraditional routes…
