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Cardiovascular diseases (CVDs) comprise a group of diseases and disorders of the heart and blood vessels, which together are the number one cause of death worldwide, being associated with multiple genetic and modifiable risk factors, and that may directly arise from different etiologies. For a long time, the search for cardiovascular drugs was based on the old paradigm "one compound - one target", aiming to obtain a highly potent and selective molecule with only one desired molecular target. Although historically successful in the last decades, this approach ignores the multiple causes and the multifactorial nature of CVDs. Thus, over time, treatment strategies for cardiovascular diseases have changed, and, currently, pharmacological therapies for CVD are mainly based on the association of two or more drugs to control symptoms and reduce cardiovascular death. In this context, the development of multitarget drugs, i.e., compounds having the ability to act simultaneously at multiple sites, is an attractive and relevant strategy that can be even more advantageous to achieve predictable pharmacokinetic and pharmacodynamics correlations as well as better patient compliance. In this review, we aim to highlight the efforts and rational pharmacological bases for the design of some promising multitargeted compounds to treat important cardiovascular diseases like heart failure, atherosclerosis, acute myocardial infarction, pulmonary arterial hypertension, and arrhythmia., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Neurodegenerative diseases trigger neuronal cell death by a variety of endogenous suicide pathways. Although cell death may occur through highly heterogeneous processes, specific cell organelles and stress sensors have shown promise as potential therapeutic targets. The plasma membrane senses stress through residing receptors, which can directly or indirectly activate apoptosis. Importantly, several events involved in neuronal death also affect mitochondria homeostasis, leading to calcium uptake, opening of the permeability transition pore, and release of apoptogenic factors. In addition, nuclear DNA damage triggers cell death, where p53 is activated to modulate the expression of selected apoptosis target genes. Signaling proteins implicated in apoptosis pathways are enriched at the Golgi complex, including death receptors and the phosphoinositide 3-kinase. Finally, neurodegenerative diseases progress with accumulation of misfolded proteins, deficiently removed by intracellular proteases or chaperones, and transport abnormalities due to disturbance of cytoskeletal organization in degenerating neurons. The challenge is to decode the complex signaling network of inter-organellar crosstalk leading to cell death and identify therapeutic approaches for delaying or preventing neurodegenerative diseases.