Characteristics of neurons

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Characteristics of neurons

• Cytoskeletal organization
• Microtubules and motors
• Neuronal intermediate filaments
• Neurofilaments
• Peripherin, Nestin
• Microfilaments
• Actins
• Axonal transport
• Fast transport
• Slow transport

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Neurofilaments (EM)
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Neurofilaments (EM)
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Neurofilaments (biochemistry)
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Neurofilaments

• Functions
• Maintenance of the axonal organization
• Radial growth
• Mechanisms
• Phosphorylation
• Glycosylation?

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Axonal growth

• Longitudinal growth
• To establish the connection with targets
• Growth cone
• Early phase of Regeneration/Development
• Actin and microtubules
• Radial growth
• To increase axonal caliber
• Late phase of Regeneration/Development
• Neurofilaments

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Neurofilaments and Axonal caliber

• Inherent neuronal characteristics
• Large targets with large axons
• Developmental stage
• Smaller caliber, less NF
• Somatofugal axonal atrophy
• Atrophy of the axons in the proximal stump after
  nerve injury
• Related to NF synthesis, transport and
  phosphorylation

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Neurofilaments and Axonal caliber(Experimental
evidence)

• Correlation between caliber and NF number
• Development
• Degeneration/Regeneration
• Genetics
• Transgenic mice to delete NFs
• Spontaneous mutant Japanese quail

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NF Spontaneous mutant

• Mutant Japanese quail
• Lack of neurofilaments in axons small axonal
  caliber
• Growth normally, with some unsteadiness
• Still susceptible to acrylamide a model of
  neurofilamentous pathology
• Mechanism mutation in NF-L with a premature stop
  codon

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Transgenic mice with no NF

• Absence of NFs due to deletion of NF-L gene
• Small caliber with absence of NFs
• Grow normally with neuronal swelling in spinal
  cords and axonal degeneration

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Transgenic mice with no NF
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Neuronal swelling in NF transgenics

• Over-expression of NFs
• NF-H, NF-M, NF-L (ref)
• Mutant or normal NFs
• Pathology
• Neuronal aggregates of NFs leading to
  neurodegeneration
• Axonal atrophy and degeneration

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Filamentous neuropathology

• NF pathology
• Neuronal
• Early stage of ALS
• Transgenics NF, SOD
• Axonal
• Proximal IDPN
• Distal 2,5-HD
• Consequence Neuronal death (Neurodegeneration)

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Filamentous pathology in neuronal cell bodies
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Filamentous pathology in proximal axons
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Wallerian degeneration

• In the stump distal to the site of nerve injury
• Degeneration of axons
• Disintegration of axonal cytoskeleton and
  organization
• Proliferation of Schwann cells
• Infiltration of macrophages

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Neuronal response in Wallerian degeneration

• Chromatolysis
• Alteration in the patterns of mRNA
• Somatofugal atrophy
• Neuronal death in some situations

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Neurodegenerative diseases

• Cortex
• Alzheimer disease
• Frontotemporal dementia
• Motor and coordination system
• Motor neuron disease, Amyotrophic lateral
  sclerosis (ALS)
• Parkinsons disease
• Spinocerebellar atrophy (SCA)
• Autonomic system
• Multiple system atrophy

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Filamentous neuropathology

• MT pathology
• Acrylamide
• NF pathology
• Neuronal
• Early stage of ALS
• Transgenics NF, SOD
• Axonal
• Proximal IDPN
• Distal 2,5-HD
• Tau pathology
• NFT in Alzheimer disease

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Alzheimer disease

• Progressive dementia, particularly over age 65
• Basal foregbrain cholinergic hypothesis
• Pathological hallmarks
• Senile plaque
• Neurofibrillary tangle

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Regenerative strategy for neurodegenerative
diseases

• Supplement of deficiency cholinergic medications
• Replacement of cells stem cells, adrenergic
  cells
• Establishment of connections repulsive and
  attractive molecules

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• ???????
• ??? (growth cones)
• ????(attractants)
• ????(repulsants)

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