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Can regional spreading of amyotrophic lateral sclerosis motor symptoms be explained by prion-like propagation?

Kanouchi T, Ohkubo T, Yokota T - J. Neurol. Neurosurg. Psychiatr. (2012)

Bottom Line: The intercellular transfer of inclusions made of tau, α-synuclein and huntingtin has been demonstrated, revealing the existence of mechanisms reminiscent of those by which prions spread through the nervous system.Evidence for such a prion-like propagation mechanism has now spread to the major misfolded proteins, superoxide dismutase 1 (SOD1) and the 43 kDa transactive response DNA binding protein (TDP-43), implicated in ALS.Furthermore, the concept of 'propagation' is dissected into contiguous and non-contiguous types, and this concept is expanded to the severity of the focal symptom as well as its regional spread which can be explained by cell to cell propagation in the local neuron pool.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology and Neurological Science, Tokyo Medical and Dental University, Tokyo, Japan.

ABSTRACT
Progressive accumulation of specific misfolded protein is a defining feature of amyotrophic lateral sclerosis (ALS), similarly seen in Alzheimer disease, Parkinson disease, Huntington disease and Creutzfeldt-Jakob disease. The intercellular transfer of inclusions made of tau, α-synuclein and huntingtin has been demonstrated, revealing the existence of mechanisms reminiscent of those by which prions spread through the nervous system. Evidence for such a prion-like propagation mechanism has now spread to the major misfolded proteins, superoxide dismutase 1 (SOD1) and the 43 kDa transactive response DNA binding protein (TDP-43), implicated in ALS. The focus in this review is on what is known about ALS progression in terms of clinical as well as molecular aspects. Furthermore, the concept of 'propagation' is dissected into contiguous and non-contiguous types, and this concept is expanded to the severity of the focal symptom as well as its regional spread which can be explained by cell to cell propagation in the local neuron pool.

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The severity of the focal symptom can be explained by local propagation. Exacerbation of hand muscle atrophy is caused by loss of α-motor neurons in the motor neuron pool in the spinal anterior horn innervating the hand muscle. Such a severity of the focal symptom also may be mediated by local cell to cell propagation between neighbouring spinal motor neurons.
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fig2: The severity of the focal symptom can be explained by local propagation. Exacerbation of hand muscle atrophy is caused by loss of α-motor neurons in the motor neuron pool in the spinal anterior horn innervating the hand muscle. Such a severity of the focal symptom also may be mediated by local cell to cell propagation between neighbouring spinal motor neurons.

Mentions: Disease progression in ALS consists of regional spread of motor symptoms and exacerbation of local motor symptoms, such as a decrease in grip strength and progression of thenar muscle atrophy. We suppose that such an exacerbation of focal motor symptoms is also explained by the contiguous propagation mechanism. For example, the severity of hand muscle atrophy is determined by the remaining number of motor neurons in the lateral nuclear group of the spinal anterior horn innervating the hand muscle after neuronal degeneration and reinnervation of the denervated muscle fibres. In this motor neuron pool of the lateral nuclear group, neuronal degeneration might be mediated by local cell to cell propagation of the disease property between spinal motor neurons proximate to each other after the seeding to a single motor neuron (figure 2). This indicates that the concept of ‘propagation’ can include exacerbation of the focal symptom as well as its regional spread.


Can regional spreading of amyotrophic lateral sclerosis motor symptoms be explained by prion-like propagation?

Kanouchi T, Ohkubo T, Yokota T - J. Neurol. Neurosurg. Psychiatr. (2012)

The severity of the focal symptom can be explained by local propagation. Exacerbation of hand muscle atrophy is caused by loss of α-motor neurons in the motor neuron pool in the spinal anterior horn innervating the hand muscle. Such a severity of the focal symptom also may be mediated by local cell to cell propagation between neighbouring spinal motor neurons.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3368493&req=5

fig2: The severity of the focal symptom can be explained by local propagation. Exacerbation of hand muscle atrophy is caused by loss of α-motor neurons in the motor neuron pool in the spinal anterior horn innervating the hand muscle. Such a severity of the focal symptom also may be mediated by local cell to cell propagation between neighbouring spinal motor neurons.
Mentions: Disease progression in ALS consists of regional spread of motor symptoms and exacerbation of local motor symptoms, such as a decrease in grip strength and progression of thenar muscle atrophy. We suppose that such an exacerbation of focal motor symptoms is also explained by the contiguous propagation mechanism. For example, the severity of hand muscle atrophy is determined by the remaining number of motor neurons in the lateral nuclear group of the spinal anterior horn innervating the hand muscle after neuronal degeneration and reinnervation of the denervated muscle fibres. In this motor neuron pool of the lateral nuclear group, neuronal degeneration might be mediated by local cell to cell propagation of the disease property between spinal motor neurons proximate to each other after the seeding to a single motor neuron (figure 2). This indicates that the concept of ‘propagation’ can include exacerbation of the focal symptom as well as its regional spread.

Bottom Line: The intercellular transfer of inclusions made of tau, α-synuclein and huntingtin has been demonstrated, revealing the existence of mechanisms reminiscent of those by which prions spread through the nervous system.Evidence for such a prion-like propagation mechanism has now spread to the major misfolded proteins, superoxide dismutase 1 (SOD1) and the 43 kDa transactive response DNA binding protein (TDP-43), implicated in ALS.Furthermore, the concept of 'propagation' is dissected into contiguous and non-contiguous types, and this concept is expanded to the severity of the focal symptom as well as its regional spread which can be explained by cell to cell propagation in the local neuron pool.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology and Neurological Science, Tokyo Medical and Dental University, Tokyo, Japan.

ABSTRACT
Progressive accumulation of specific misfolded protein is a defining feature of amyotrophic lateral sclerosis (ALS), similarly seen in Alzheimer disease, Parkinson disease, Huntington disease and Creutzfeldt-Jakob disease. The intercellular transfer of inclusions made of tau, α-synuclein and huntingtin has been demonstrated, revealing the existence of mechanisms reminiscent of those by which prions spread through the nervous system. Evidence for such a prion-like propagation mechanism has now spread to the major misfolded proteins, superoxide dismutase 1 (SOD1) and the 43 kDa transactive response DNA binding protein (TDP-43), implicated in ALS. The focus in this review is on what is known about ALS progression in terms of clinical as well as molecular aspects. Furthermore, the concept of 'propagation' is dissected into contiguous and non-contiguous types, and this concept is expanded to the severity of the focal symptom as well as its regional spread which can be explained by cell to cell propagation in the local neuron pool.

Show MeSH
Related in: MedlinePlus