Traffic signaling: new functions of huntingtin and axonal transport in neurological disease

@article{Vitet2020TrafficSN,
  title={Traffic signaling: new functions of huntingtin and axonal transport in neurological disease},
  author={H{\'e}l{\`e}ne Vitet and Vicky Brandt and Fr{\'e}d{\'e}ric Saudou},
  journal={Current Opinion in Neurobiology},
  year={2020},
  volume={63},
  pages={122-130}
}
Over the past twenty years there have been numerous advances in our understanding of Huntington's disease (HD) and other neurodegenerative proteopathies such as Alzheimer's disease and Parkinson's disease. In each case, disease-specific proteins are expressed and accumulate; what has been less clear is precisely what problems are caused by the accumulation. Recently we have begun to appreciate that increased protein levels or changes in the ratios of different isoforms affect the movement of… 
10 Citations
Mitochondrial Abnormalities and Synaptic Damage in Huntington's Disease: a Focus on Defective Mitophagy and Mitochondria-Targeted Therapeutics.
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Recent research in Huntington's disease progression is discussed, including developments of cell and mouse models, cellular changes, mitochondrial abnormalities, DNA damage, bioenergetics, oxidative stress, mitophagy, and therapeutics strategies in HD.
When Good Kinases Go Rogue: GSK3, p38 MAPK and CDKs as Therapeutic Targets for Alzheimer’s and Huntington’s Disease
  • S. D’Mello
  • Medicine
    International journal of molecular sciences
  • 2021
TLDR
This review covers what is known about the role of these three groups of kinases in the brain and in the pathogenesis of the two neurodegenerative disorders and the potential of targeting GSK3, p38 MAPK and CDKS as effective therapeutics.
A possible non-proteolytic role of ubiquitin conjugation in alleviating the pathology of Huntingtin’s aggregation
TLDR
The results suggest that the E6-AP ubiquitin ligase reduces nuclear inclusion frequency while accelerating polyglutamine-induced pathology in SCA1 mice, and the emerging role of the first 17 amino acids of huntingtin in Huntington’s disease is underestimated.
Huntingtin and the Synapse
TLDR
It is argued that wtHTT loss is not well-tolerated at the synaptic level, and it is concluded that wTHTT presence is essential for proper synaptic function.
Huntingtin-lowering strategies for Huntington’s disease
ABSTRACT Introduction Huntington’s disease (HD) is an incurable, autosomal dominant neurodegenerative disease caused by an abnormally long polyglutamine tract in the huntingtin protein. Because this
Huntingtin structure is orchestrated by HAP40 and shows a polyglutamine expansion-specific interaction with exon 1
TLDR
The exon 1 region of HTT is dynamic but shows greater conformational variety in the polyglutamine expanded mutant than wildtype exon 2, and Native mass spectrometry reveals a remarkably stable hetero-dimer, potentially explaining the cellular inter-dependence ofHTT and HAP40.
HAP40 orchestrates huntingtin structure for differential interaction with polyglutamine expanded exon 1
TLDR
The polyglutamine tract containing N-terminal exon 1 region of HTT is dynamic, but shows greater conformational variety in the mutant than wildtype exon 2, and Native mass-spectrometry reveals a remarkably stable hetero-dimer, potentially explaining the cellular inter-dependence ofHTT and HAP40.
Presynaptic protein synthesis and brain plasticity: From physiology to neuropathology
TLDR
Here, a growing body of evidence is reviewed that local protein synthesis in discrete sites of the axon and presynaptic terminals plays crucial roles in synaptic plasticity, and that deregulation of this local translation system is implicated in various pathologies of the nervous system.
Blood-Brain Barrier Dysfunction in CNS Disorders and Putative Therapeutic Targets: An Overview
TLDR
The fundamental structure and function of the blood-brain barrier is described in both healthy and altered/diseased conditions and the potential therapeutic targets that could be leveraged to restore the integrity of the BBB concomitant to the treatment of these brain disorders are provided.

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