TABLE I. Neurodegenerative diseases linked to defects in axonal transport.

Disease	Clinical Features*	Genetics	Proteins Implicated	Axonal Transport Disrupted?	Evidence	Ref
Amyotrophic Lateral Sclerosis	Upper+ and Lower++ motor neuron	Multi-factorial	SOD1	Yes	Mutant SOD1 expression inhibits axonal transport early in disease.	[17, 3]
Huntington's Disease	Chorea, psychiatric and cognitive dysfunction	Autosomal dominant	Huntingtin	Yes	Expression of the pathogenic HTT causes axonal transport defects in fly models. Striatal neurons are selectively vulnerable to transport defects induced by mutant HTT in mouse models.	[18,101]
Alzheimer's Disease	Memory impairment, dementia	Multi-factorial	Tau, amyloid-β	Yes	Axonal swellings observed in mouse and fly models. Reductions in kinesin I promote amyloid deposition.	[102]
Parkinson's Disease	Rest tremor, rigidity, bradykinesia and gait disturbance	Multi-factorial	α-synuclein	Yes	α-synuclein mutants associated with PD induce reduced transport in cultured neurons.	[21]
Hereditary Motor Neuropathy, type VIIB (HMN7B) [also known as distal Spinal and Bulbar Muscular Atrophy (dSBMA)]	Lower motor neuron+ (hands>feet), prominent bulbar symptoms	Autosomal dominant	p150Glued	Not significantly affected	No significant defects observed in sciatic nerve ligation assays, but organelle accumulations observed in motor neurons in mice expressing mutant p150Glued.	[13,15]
Perry Syndrome	Parkinsonism, weight loss, hypoventilation, depression	Autosomal dominant	p150Glued	Not determined	Mutations recently characterized	[16]
Charcot –Marie-Tooth, type 2B	Length-dependent sensory and motor axonal neuropathy	Autosomal dominant	Rab 7	Equivocal	Rab7 recruits effectors and/or motors to late endosomes/lysosomes.	[32]
Charcot–Marie-Tooth, type 2A	Length-dependent sensory and motor axonal neuropathy	Autosomal dominant	Kinesin (KIF1B)	Equivocal	Decreased synaptic vesicle proteins in sciatic nerve extracts of KIF1B-/-□mice.	[103]
Hereditary Spastic Paraplegia, type 10	Lower extremity weakness and spasticity	Autosomal dominant	Kinesin (KIF5A)	Equivocal	Slower cargo velocity in-vitro	[104]

^*Represents classical disease features.

⁺Upper motor neurons features include: weakness, hyperreflexia, and spasticity

⁺⁺Lower motor neuron features include: weakness, muscle atrophy and fasciculations

SOD1 (superoxide dismutase), HTT (huntingtin)