Molecular Targeted Therapy

Publication Title: 
Medical Hypotheses

A synergistic-healing strategy that combines molecular targeting within a system-wide perspective is presented as the Multiple Integrated Complementary Healing Approaches: Energetics And Light (MICHAEL). The basis of the MICHAEL approach is the realization that environmental, nutritional and electromagnetic factors form a regulatory framework involved in bone and nerve healing. The interactions of light, energy, and nutrition with neural, hormonal and cellular pathways will be presented.

Author(s): 
Gray, Michael G.
Lackey, Brett R.
Patrick, Evelyn F.
Gray, Sandra L.
Hurley, Susan G.
Publication Title: 
EMBO molecular medicine

Sirtuins are NAD-dependent protein deacetylases known to have protective effects against age-related diseases such as cancer, diabetes, cardiovascular and neurodegenerative diseases. In mammals, there are seven sirtuins (SIRT1-7), which display diversity in subcellular localization and function. While SIRT1 has been extensively investigated due to its initial connection with lifespan extension and involvement in calorie restriction, important biological and therapeutic roles of other sirtuins have only recently been recognized.

Author(s): 
Donmez, Gizem
Outeiro, Tiago F.
Publication Title: 
The Journal of Clinical Investigation

Rapamycin, an inhibitor of mechanistic target of rapamycin (mTOR), has the strongest experimental support to date as a potential anti-aging therapeutic in mammals. Unlike many other compounds that have been claimed to influence longevity, rapamycin has been repeatedly tested in long-lived, genetically heterogeneous mice, in which it extends both mean and maximum life spans. However, the mechanism that accounts for these effects is far from clear, and a growing list of side effects make it doubtful that rapamycin would ultimately be beneficial in humans.

Author(s): 
Lamming, Dudley W.
Ye, Lan
Sabatini, David M.
Baur, Joseph A.
Publication Title: 
Neurobiology of Aging

Accumulation of the transactive response DNA-binding protein 43 (TDP-43) is a major hallmark of several neurodegenerative disorders, collectively known as TDP-43 proteinopathies. The most common TDP-43 proteinopathies, frontotemporal lobar degeneration with TDP-43-positive inclusions, and amyotrophic lateral sclerosis, share overlapping neuropathological and clinical phenotypes. The development and detailed analysis of animal models of TDP-43 proteinopathies are critical for understanding the pathogenesis of these disorders.

Author(s): 
Medina, David X.
Orr, Miranda E.
Oddo, Salvatore
Publication Title: 
Neurobiology of Aging

Silent information regulator 1 (SIRT1) is a type of histone deacetylase whose activity is dependent on nicotinamide adenine dinucleotide. SIRT1 plays a key role in the longevity effects elicited by calorie restriction. Recently, a neuroprotective effect of SIRT1 was reported for neurological diseases. The focus of this review is to summarize the protective effects of SIRT1 in cerebral ischemia. First, the posttranslational modifications of SIRT1 are illustrated; then, we discuss the roles of SIRT1 in cerebral immune homeostasis.

Author(s): 
Yang, Yang
Duan, Weixun
Li, Yue
Yan, Juanjuan
Yi, Wei
Liang, Zhenxing
Wang, Ning
Yi, Dinghua
Jin, Zhenxiao
Publication Title: 
Nature Communications

The growing availability of 'omics' data and high-quality in silico genome-scale metabolic models (GSMMs) provide a golden opportunity for the systematic identification of new metabolic drug targets. Extant GSMM-based methods aim at identifying drug targets that would kill the target cell, focusing on antibiotics or cancer treatments. However, normal human metabolism is altered in many diseases and the therapeutic goal is fundamentally different--to retrieve the healthy state. Here we present a generic metabolic transformation algorithm (MTA) addressing this issue.

Author(s): 
Yizhak, Keren
Gabay, Orshay
Cohen, Haim
Ruppin, Eytan
Publication Title: 
Trends in Pharmacological Sciences

Recent studies in mice have identified single molecules that can delay multiple diseases of aging and extend lifespan. In theory, such molecules could prevent dozens of diseases simultaneously, potentially extending healthy years of life. In this review, we discuss recent advances, controversies, opportunities, and challenges surrounding the development of SIRT1 activators, molecules with the potential to delay aging and age-related diseases. Sirtuins comprise a family of NAD?-dependent deacylases that are central to the body's response to diet and exercise.

Author(s): 
Hubbard, Basil P.
Sinclair, David A.
Publication Title: 
Neuropharmacology

It is becoming increasingly clear that a dysfunction of the GABAergic/glutamatergic network in telencephalic brain structures may be the pathogenetic mechanism underlying psychotic symptoms in schizophrenia (SZ) and bipolar (BP) disorder patients. Data obtained in Costa's laboratory (1996-2009) suggest that this dysfunction may be mediated primarily by a downregulation in the expression of GABAergic genes (e.g., glutamic acid decarboxylase??[GAD??] and reelin) associated with DNA methyltransferase (DNMT)-dependent hypermethylation of their promoters.

Author(s): 
Guidotti, A.
Auta, J.
Chen, Y.
Davis, J. M.
Dong, E.
Gavin, D. P.
Grayson, D. R.
Matrisciano, F.
Pinna, G.
Satta, R.
Sharma, R. P.
Tremolizzo, L.
Tueting, P.
Publication Title: 
Molecular Psychiatry

Neurogenetics research has begun to advance our understanding of how genetic variation gives rise to individual differences in brain function, which, in turn, shapes behavior and risk for psychopathology. Despite these advancements, neurogenetics research is currently confronted by three major challenges: (1) conducting research on individual variables with small effects, (2) absence of detailed mechanisms, and (3) a need to translate findings toward greater clinical relevance.

Author(s): 
Bogdan, R.
Hyde, L. W.
Hariri, A. R.
Publication Title: 
Molecular bioSystems

Psychiatric disorders affect approximately 10% of adults in North-America. The complex nature of these illnesses makes the search for their pathophysiology a challenge. However, studies have consistently shown that mitochondrial dysfunction and oxidative stress are common features across major psychiatric disorders, including bipolar disorder and schizophrenia. Nevertheless, little is known about specific targets of oxidation in the brain.

Author(s): 
Andreazza, Ana Cristina

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