Abstract
More than 5.5 million Americans of all ages are suffering from Alzheimer's disease (AD) till today for which no suitable therapy has been developed so far. Thus, there is an urgent need to explore novel therapeutic measures to contain brain pathology in AD. The hallmark of AD includes amyloid-beta peptide (AβP) deposition and phosphorylation of tau in AD brain. Recent evidences also suggest a marked decrease in neurotrophic factors in AD. Thus, exogenous supplement of neurotrophic factors could be one of the possible ways for AD therapy. Human postmortem brain in AD shows alterations in histamine receptors as well, indicating an involvement of the amine in AD-induced brain pathology. In this review, we focused on role of histamine 3 and 4 receptor-modulating drugs in the pathophysiology of AD. Moreover, antibodies to histamine and tau appear to be also beneficial in reducing brain pathology, blood–brain barrier breakdown, and edema formation in AD. Interestingly, TiO2-nanowired delivery of cerebrolysin-a balanced composition of several neurotrophic factors attenuated AβP deposition and reduced tau phosphorylation in AD brain leading to neuroprotection. Coadministration of cerebrolysin with histamine antibodies or tau antibodies has further enhanced neuroprotection in AD. These novel observations strongly suggest a role of nanomedicine in AD that requires further investigation.
| Original language | English (US) |
|---|---|
| Title of host publication | International Review of Neurobiology |
| Publisher | Academic Press Inc |
| Pages | 123-165 |
| Number of pages | 43 |
| DOIs | |
| State | Published - 2017 |
Publication series
| Name | International Review of Neurobiology |
|---|---|
| Volume | 137 |
| ISSN (Print) | 0074-7742 |
| ISSN (Electronic) | 2162-5514 |
Funding
Supported by grants from the Air Force Office of Scientific Research (EOARD, London, UK) and Air Force Material Command, USAF, under Grant No. FA8655-05-1-3065; supported by Grants from the Alzheimer's Association (IIRG-09-132087), the National Institutes of Health (R01 AG028679), and the Dr. Robert M. Kohrman Memorial Fund (MAS, R.J.C.); Swedish Medical Research Council (Nr 2710, H.S.S.), Göran Gustafsson Foundation, Stockholm, Sweden (H.S.S.), Astra Zeneca, Mölndal, Sweden (H.S.S./A.S.), The University Grants Commission, New Delhi, India (H.S.S./A.S.), Ministry of Science & Technology, Govt. of India (H.S.S./A.S.), Indian Medical Research Council, New Delhi, India (H.S.S./A.S.) and India-EU Co-operation Program (R.P./A.S./H.S.S.) and IT 794/13 (J.V.L.), Government of Basque Country and UFI 11/32 (J.V.L.) University of Basque Country, Spain, & Society for Neuroprotection and Neuroplasticity (SSNN), Romania. Technical and human support provided by Dr. Ricardo Andrade from SGIker (UPV/EHU) is gratefully acknowledged. We thank Suraj Sharma, Uppsala, Sweden for computer and graphic support. The US Government is authorized to reproduce and distribute reprints for Government purpose notwithstanding any copyright notation thereon. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsements, either expressed or implied, of the Air Force Office of Scientific Research or the US Government.
Keywords
- 3 receptor
- Alzheimer's disease
- Blood–brain barrier
- Brain edema
- Cerebrolysin
- Histamine
- Histamine 4 receptor
- Neuroprotection
- TiO-nanowired delivery
- p-tau antibodies
ASJC Scopus subject areas
- Clinical Neurology
- Cellular and Molecular Neuroscience
