Addressing Alzheimers Disease Tangles: From NAP to AL-108
- Resource Type
- Authors
- Alistair J Stewart; Illana Gozes; Donald E. Schmechel; Karole Sutherland; Anthony W. Fox; Bruce H. Morimoto
- Source
- Current Alzheimer Research. 6:455-460
- Subject
- Nerve Tissue Proteins
tau Proteins
Disease
Microtubules
Neuroprotection
Mice
Memory
In vivo
mental disorders
medicine
Animals
Humans
Administration, Intranasal
Homeodomain Proteins
Clinical Trials as Topic
Neurodegeneration
Brain
Neurofibrillary Tangles
medicine.disease
In vitro
Nap
Neurology
Mechanism of action
Neurology (clinical)
medicine.symptom
Alzheimer's disease
Cognition Disorders
Psychology
Oligopeptides
Neuroscience
psychological phenomena and processes
- Language
- ISSN
- 1567-2050
AL-108 is the intranasal formulation of NAP (a peptide of eight amino acids, NAPVSIPQ). Phase IIa clinical results have recently shown that AL-108 has a positive impact on memory function in patients with amnestic mild cognitive impairment (aMCI), a precursor to Alzheimer's disease (AD). The clinical development of AL-108 has been based on extensive studies showing pre-clinical efficacy for NAP. NAP has demonstrated potent neuroprotective activity in vitro and in vivo. Its mechanism of action is thought to center on the modulation of microtubule stability in the face of outside damage. Such an effect on structures of such central importance in a broad range of cellular functions is thought to explain NAP's activity in wide ranging models of cellular damage and neurodegeneration. The following article reviews NAP's discovery and pharmacological characterization that has led to clinical development of a novel tangle-directed drug candidate.