Common threads in neurodegenerative disorders of aging

  title={Common threads in neurodegenerative disorders of aging},
  author={M. Flint Beal and Ella Bossy‐Wetzel and Steven Finkbeiner and Gary Fiskum and Benoit I. Giasson and Carl Johnson and Zaven S. Khachaturian and Virginia M. -Y. Lee and David Nicholls and Hemachandra Reddy and Ian Reynolds and David B. Teplow and Leon Thal and John Q. Trojanowski and Dominic M. Walsh and Ronald Wetzel and Nancy S Wexler and Anne B. Young and Lisa J Bain},
  journal={Alzheimer's \& Dementia},

Predicting fates in models of neurodegenerative disease: longitudinal measures of protein homeostasis in live neurons

A new strategy that combines robotic microscopy and longitudinal analysis to quantitatively measure the relationship between intermediate disease-associated changes in a neuron and its ultimate fate at a single-cell level is developed, suggesting a simple unifying model of neurodegeneration.

Using stable isotope labeling to advance our understanding of Alzheimer’s disease etiology and pathology

These stable isotope‐MS methodologies offer new opportunities to study proteome changes in AD and other neurodegenerative diseases by elucidating mechanisms to target for treatment and prevention.

Morphological remodeling of C. elegans neurons during aging is modified by compromised protein homeostasis

It is found that proteostatic challenges conferred by polyQ-expanded Htt and knockdown of specific genes involved in protein homeostasis can lead to morphological changes that are restricted to specific domains of specific neurons.

The Autophagy Lysosomal Pathway and Neurodegeneration.

  • S. Finkbeiner
  • Biology
    Cold Spring Harbor perspectives in biology
  • 2019
This review focuses on recent advances in the understanding of the autophagy lysosomal pathway and its potential relationship to the pathogenesis and treatment of neurodegenerative diseases.

Protein Quality Control in Neurodegenerative Diseases

The stresssensing mechanisms that regulate HSFs and the role of post-translational modifications that regulateHSF activity are examined and the expression of molecular chaperones and heat shock genes is important for development.



Common mechanisms of amyloid oligomer pathogenesis in degenerative disease

  • C. Glabe
  • Biology
    Neurobiology of Aging
  • 2006

Mitochondria take center stage in aging and neurodegeneration

  • M. Beal
  • Biology
    Annals of neurology
  • 2005
There is strong evidence from genetics and transgenic mouse models that mitochondrial dysfunction results in neurodegeneration and may contribute to the pathogenesis of Alzheimer’s disease, Parkinson's disease, Huntington's Disease, amyotrophic lateral sclerosis, hereditary spastic paraplegia, and cerebellar degenerations.

Neurodegenerative diseases: new concepts of pathogenesis and their therapeutic implications.

A perspective on pathogenesis suggests that a wide variety of neurodegenerative diseases can be grouped mechanistically as brain amyloidoses, an outlook that yields novel insights into potential therapeutic approaches that may be applicable across the broad spectrum of neuro degenerative disease.

What is the role of protein aggregation in neurodegeneration?

It is suggested that protein aggregation is pathogenic, but several lines of evidence indicate that inclusion bodies are not the main cause of toxicity, and probably represent a cellular protective response.

Nitric oxide‐induced mitochondrial fission is regulated by dynamin‐related GTPases in neurons

It is reported that mitochondria undergo profound fission in response to nitric oxide in cortical neurons of primary cultures and persistent mitochondrial fission may play a causal role in NO‐mediated neurotoxicity.

In Situ Respiration and Bioenergetic Status of Mitochondria in Primary Cerebellar Granule Neuronal Cultures Exposed Continuously to Glutamate*

It is concluded that excitotoxicity under these conditions is not because of an ATP deficit or uncoupling, and mitochondria maintain the same respiratory capacity as in control cells.

Automated microscope system for determining factors that predict neuronal fate.

An automated imaging and analysis system that enables us to follow the fates of individual cells and intracellular proteins over time and adapted survival analysis methods to determine whether and how factors measured during longitudinal analysis predict a particular biological outcome are determined.