Targeting New Candidate Genes by Small Molecules Approaching Neurodegenerative Diseases

Fan, Hueng Chuen; Shiang, Ching; Cheng, Shu‐Meng; Lee, Hsiu Fen; Tsai, Jeng Dau; Lin, Shinn Zong; Harn, Horng Jyh

doi:10.3390/ijms17010026

Cited by 8 publications

(5 citation statements)

References 215 publications

(240 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(v) Novel, diverse targets reducing muHTT production, enhancing muHTT degradation, and generally lowering muHTT-conferred (long-term) toxicity, and thus, positively affect HD onset and progression. These targets include CASPs [ 2 , 14 , 15 , 17 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 79 ], HSPs [ 2 , 22 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ], HDACs [ 2 , 14 , 15 , 17 , 20 , 79 , 105 ], PDEs [ 14 , 15 , 17 , 31 , 35 , 36 ], and σRs [ 14 , 15 , 35 , 37 , 79 ], but also the adenosine 2A receptor (A2AR) [ 14 , 36 ], the AMP-activated protein kinase (AMPK) [ 20 , 31 , 79 ], the ERG-associated protein with SET domain (ESET) [ 106 , 107 , 108 ], the Kelch-like ECH-associated protein (KEAP) [ 31 , 56 , 109 ,…”

Section: Resultsmentioning

confidence: 99%

A Novel Huntington’s Disease Assessment Platform to Support Future Drug Discovery and Development

Möhle

Brüning

et al. 2022

IJMS

View full text Add to dashboard Cite

Huntington’s disease (HD) is a lethal neurodegenerative disorder without efficient therapeutic options. The inefficient translation from preclinical and clinical research into clinical use is mainly attributed to the lack of (i) understanding of disease initiation, progression, and involved molecular mechanisms; (ii) knowledge of the possible HD target space and general data awareness; (iii) detailed characterizations of available disease models; (iv) better suitable models; and (v) reliable and sensitive biomarkers. To generate robust HD-like symptoms in a mouse model, the neomycin resistance cassette was excised from zQ175 mice, generating a new line: zQ175Δneo. We entirely describe the dynamics of behavioral, neuropathological, and immunohistological changes from 15–57 weeks of age. Specifically, zQ175Δneo mice showed early astrogliosis from 15 weeks; growth retardation, body weight loss, and anxiety-like behaviors from 29 weeks; motor deficits and reduced muscular strength from 36 weeks; and finally slight microgliosis at 57 weeks of age. Additionally, we collected the entire bioactivity network of small-molecule HD modulators in a multitarget dataset (HD_MDS). Hereby, we uncovered 358 unique compounds addressing over 80 different pharmacological targets and pathways. Our data will support future drug discovery approaches and may serve as useful assessment platform for drug discovery and development against HD.

show abstract

Section: Resultsmentioning

confidence: 99%

A Novel Huntington’s Disease Assessment Platform to Support Future Drug Discovery and Development

Möhle

Brüning

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…These diseases including Huntington's disease (HD), Alzheimer's disease (AD), Parkinson's disease (PD), etc. [[61], [62], [63]]. A common feature of these neurological diseases is delayed neurological symptoms and degeneration, which preferentially affect nerve cells in the brain.…”

Section: Genome Editing For Disease Modelingmentioning

confidence: 99%

Applications of Genome Editing Technology in Animal Disease Modeling and Gene Therapy

Zhou

Wang

et al. 2019

Computational and Structural Biotechnology Journal

View full text Add to dashboard Cite

Genome editing technology is a technique for targeted genetic modifications, enabling the knockout and addition of specific DNA fragments. This technology has been widely used in various types of biomedical research, clinics and agriculture. In terms of disease research, constructing appropriate animal models is necessary. Combining reproductive technology with genome editing, many animal disease models have been generated for basic and clinical research. In addition, precisely targeted modifications allow genome editing to flourish in the field of gene therapy. Many mutations refractory to traditional gene therapy could be permanently corrected at the DNA level. Thus, genome editing is undoubtedly a promising technology for gene therapy. In this review, we mainly introduce the applications of genome editing in constructing animal disease models and gene therapies, as well as its future prospects and challenges.

show abstract

“…A number of cardiovascular disease such as hypertension could also lead to stroke and results in significant neuronal changes and/or death [66]. The common pathology of NDs involve oxidative stress and inflammatory cascades through orchestrated cell-cell interaction including the immune cells in the central nervous system, such as the microglia [67].…”

Section: Hallmark Of Neurodegeneration: Protein Misfolding and Precipitationmentioning

confidence: 99%

Targeting mTORs by omega-3 fatty acids: A possible novel therapeutic strategy for neurodegeneration?

Shirooie

Nabavi

Dehpour

et al. 2018

Pharmacological Research

View full text Add to dashboard Cite

Neurodegenerative diseases (NDs) such as Parkinson's (PD), Alzheimer's (AD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) cause significant world-wide morbidity and mortality. To date, there is no drug of cure for these, mostly age-related diseases, although approaches in delaying the pathology and/or giving patients some symptomatic relief have been adopted for the last few decades. Various studies in recent years have shown the beneficial effects of omega-3 poly unsaturated fatty acids (PUFAs) through diverse mechanisms including anti-inflammatory effects. This review now assesses the potential of this class of compounds in NDs therapy through specific action against the mammalian target of rapamycin (mTOR) signaling pathway. The role of mTOR in neurodegenerative diseases and targeted therapies by PUFAs are discussed.

show abstract

Targeting New Candidate Genes by Small Molecules Approaching Neurodegenerative Diseases

Cited by 8 publications

References 215 publications

A Novel Huntington’s Disease Assessment Platform to Support Future Drug Discovery and Development

A Novel Huntington’s Disease Assessment Platform to Support Future Drug Discovery and Development

Applications of Genome Editing Technology in Animal Disease Modeling and Gene Therapy

Targeting mTORs by omega-3 fatty acids: A possible novel therapeutic strategy for neurodegeneration?

Contact Info

Product

Resources

About