Related Experiment Video

Updated: May 22, 2026

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species
07:08

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species

Published on: February 27, 2018

Energy dysfunction in Huntington's disease: insights from PGC-1α, AMPK, and CKB

Tz-Chuen Ju1, Yow-Sien Lin, Yijuang Chern

  • 1Division of Neuroscience, Institute of Biomedical Sciences, Academia Sinica, Nankang, Taipei 11529, Taiwan.

Cellular and Molecular Life Sciences : CMLS
|May 26, 2012
PubMed

Insights

Huntington's disease (HD) involves a CAG repeat expansion, leading to cellular dysfunction and neurodegeneration. This review explores how disruptions in energy homeostasis, particularly involving key molecular determinants, contribute to HD pathogenesis.

Area of Science:

  • Neuroscience
  • Genetics
  • Molecular Biology

Background:

  • Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder.
  • It stems from a CAG trinucleotide expansion in the Huntingtin (Htt) gene, resulting in a polyglutamine-expanded Htt protein.
  • This expansion leads to cytotoxicity, affecting cellular machinery and causing progressive symptoms like movement disorders, cognitive decline, and dementia.

Purpose of the Study:

  • To review the role of cellular energy homeostasis in HD pathogenesis.
  • To highlight three key molecular determinants of energy regulation: peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), AMP-activated protein kinase (AMPK), and creatine kinase B (CKB).
  • To discuss the potential involvement of these factors in HD.

Main Methods:

  • Literature review focusing on recent studies.
  • Analysis of molecular mechanisms underlying energy dysregulation in HD.
  • Examination of the roles of PGC-1α, AMPK, and CKB in cellular energy homeostasis and their connection to HD.

Main Results:

  • HD is characterized by significant brain atrophy, particularly in the striatum and cortex.
  • Beyond neuronal defects, mitochondrial dysfunction and altered energy homeostasis are increasingly recognized as critical in HD progression.
  • Dysregulation of PGC-1α, AMPK, and CKB may represent important pathogenic pathways in HD.

Conclusions:

  • Energy dysregulation is a significant factor in Huntington's disease pathogenesis.
  • Investigating the roles of PGC-1α, AMPK, and CKB offers potential therapeutic targets for HD.
  • Further research into these molecular determinants is crucial for understanding and treating HD.

More Related Videos

Single Synapse Indicators of Glutamate Release and Uptake in Acute Brain Slices from Normal and Huntington Mice08:27

Single Synapse Indicators of Glutamate Release and Uptake in Acute Brain Slices from Normal and Huntington Mice

Published on: March 11, 2020

Efficient and Scalable Production of Full-length Human Huntingtin Variants in Mammalian Cells using a Transient Expression System10:52

Efficient and Scalable Production of Full-length Human Huntingtin Variants in Mammalian Cells using a Transient Expression System

Published on: December 10, 2021

Related Concept Videos

Huntington Disease l: Introduction01:21

Huntington Disease l: Introduction

Huntington disease or HD is a progressive, fatal neurodegenerative disorder inherited in an autosomal dominant pattern.PathophysiologyIt is caused by expansion of the CAG trinucleotide repeat in the HTT gene on chromosome 4 (4p16.3), producing an abnormal huntingtin protein with an expanded polyglutamine tract. This misfolded protein disrupts cellular function, leading to neuronal death. Normal alleles have ≤26 repeats, 27–35 are intermediate (risk of expansion), 36–39 show reduced penetrance,...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
Parkinson Disease ll: Pathophysiology01:24

Parkinson Disease ll: Pathophysiology

Parkinson disease (PD) is a progressive neurodegenerative disorder primarily affecting movement, with additional non-motor features. Its pathophysiology involves complex interactions among genetic susceptibility, environmental exposures, and cellular dysfunction, including dopaminergic neuron loss, protein aggregation, and mitochondrial impairment.Selective NeurodegenerationA key feature is the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to reduced...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...