The Role of FKBPs in Complex Disorders: Neuropsychiatric Diseases, Cancer, and Type 2 Diabetes Mellitus.

Stress is a common denominator of complex disorders and the FK-506 binding protein (FKBP)51 plays a central role in stress. Hence, it is not surprising that multiple studies imply the involvement of the FKBP51 protein and/or its coding gene, , in complex disorders. This review summarizes such reports concentrating on three disorder clusters-neuropsychiatric, cancer, and type 2 diabetes mellitus (T2DM).

The Effect of Global Warming on Complex Disorders (Mental Disorders, Primary Hypertension, and Type 2 Diabetes).

Multiple studies imply a strong relationship between global warming (GW) and complex disorders. This review summarizes such reports concentrating on three disorders-mental disorders (MD), primary hypertension, and type 2 diabetes (T2D). We also attempt to point at potential mechanisms mediating the effect of GW on these disorders.

Neuroinflammation as a Common Denominator of Complex Diseases (Cancer, Diabetes Type 2, and Neuropsychiatric Disorders).

The term neuroinflammation refers to inflammation of the nervous tissue, in general, and in the central nervous system (CNS), in particular. It is a driver of neurotoxicity, it is detrimental, and implies that glial cell activation happens prior to neuronal degeneration and, possibly, even causes it. The inflammation-like glial responses may be initiated in response to a variety of cues such as infection, traumatic brain injury, toxic metabolites, or autoimmunity.

Do Autophagy Enhancers/ROS Scavengers Alleviate Consequences of Mild Mitochondrial Dysfunction Induced in Neuronal-Derived Cells?

Mitochondrial function is at the nexus of pathways regulating synaptic-plasticity and cellular resilience. The involvement of brain mitochondrial dysfunction along with increased reactive oxygen species (ROS) levels, accumulating mtDNA mutations, and attenuated autophagy is implicated in psychiatric and neurodegenerative diseases. We have previously modeled mild mitochondrial dysfunction assumed to occur in bipolar disorder (BPD) using exposure of human neuronal cells (SH-SY5Y) to rotenone (an inhibitor of mitochondrial-respiration complex-I) for 72 and 96 h, which exhibited up- and down-regulation of mitochondrial respiration, respectively.

Is There Justification to Treat Neurodegenerative Disorders by Repurposing Drugs? The Case of Alzheimer's Disease, Lithium, and Autophagy.

Lithium is the prototype mood-stabilizer used for acute and long-term treatment of bipolar disorder. Cumulated translational research of lithium indicated the drug's neuroprotective characteristics and, thereby, has raised the option of repurposing it as a drug for neurodegenerative diseases. Lithium's neuroprotective properties rely on its modulation of homeostatic mechanisms such as inflammation, mitochondrial function, oxidative stress, autophagy, and apoptosis.

Mitochondrial function parameters as a tool for tailored drug treatment of an individual with psychosis: a proof of concept study.

Pharmacological treatment of mental disorders is currently decided based on "trial and error" strategy. Mitochondrial multifaceted dysfunction is assumed to be a major factor in the pathophysiology and treatment of schizophrenia (SZ) and bipolar disorder (BD). This study aimed to explore the feasibility of using a profile of mitochondrial function parameters as a tool to predict the optimal drug for an individual patient (personalized medicine).

Dual Role of Autophagy in Diseases of the Central Nervous System.

Autophagy is a vital lysosomal degradation and recycling pathway in the eukaryotic cell, responsible for maintaining an intricate balance between cell survival and cell death, necessary for neuronal survival and function. This dual role played by autophagy raises the question whether this process is a protective or a destructive pathway, the contributor of neuronal cell death or a failed attempt to repair aberrant processes? Deregulated autophagy at different steps of the pathway, whether excessive or downregulated, has been proposed to be associated with neurodegenerative disorders such as Alzheimer's-, Huntington's-, and Parkinson's-disease, known for their intracellular accumulation of protein aggregates. Recent observations of impaired autophagy also appeared in psychiatric disorders such as schizophrenia and bipolar disorder suggesting an additional contribution to the pathophysiology of mental illness.