Navigation Links
Mitochondria could be a target for therapeutic strategy for Alzheimer's disease patients
Date:11/5/2008

New York (Sept. 21, 2008) A study in the Sept. 21 on-line edition of Nature Medicine describes the function and interaction of a critical molecule involved in cell death in Alzheimer's disease patients. These new findings reveal that blocking this molecule, called Cyclophilin D (CypD), and development of surrounding mitochondrial targets may be viable therapeutic strategies for the prevention and treatment of Alzheimer's disease, according to Shi Du Yan, Ph.D., professor of clinical pathology in the Department's of Pathology and Surgery and in the Taub Institute for Research on Alzheimer's Disease and the Aging Brain at Columbia University Medical Center, who led the multi-center research.

This paper strengthens the concept that mitochondrial permeability pores may be central in mitochondrial and neuronal malfunction relevant to Alzheimer disease. Dr. Yan and her colleagues offer new insights into the mechanism underlying amyloid beta (Aβ)-mediated mitochondrial stress through an interaction with CypD, which is linked to synaptic plasticity and learning/memory. Importantly, these findings may help explain the mechanism of action of a medication already in use in clinical trials.

Mitochondria, the microscopic parts found outside the nucleus of the cell that produce a cell's energy, are central players in mediating neuronal stress relevant to the pathogenesis or development of neurodegenerative diseases such as Alzheimer's disease. Mitochondrial dysfunction, or a problem with the cellular exchange of energy, is an early event observed in Alzheimer's disease. Recent studies have provided substantial evidence that mitochondria serve as direct targets for amyloid beta (Aβ) protein mediated neuronal toxicity. The observations that Aβ progressively accumulates in cortical mitochondria from Alzheimer's disease patients and in brains from transgenic Alzheimer's disease type mouse models suggest the role of mitochondrial Aβ in the pathogenesis or development of the disease. This Nature Medicine study describes how this mitochondrial process may be linked to synaptic failure in Alzheimer's disease.

The study provides new insights into the mechanism underlying mitochondrial Aβ-mediated and synaptic stress that links to the mitochondrial permeability transition pore (mPTP), an opening that leads to cell death for those with Alzheimer's. Mitochondrial permeability transition pore causes mitochondrial swelling, outer membrane rupture and release of cell death mediators and enhances production of reactive oxygen species (ROS). Cyclophilin D (CypD), a type of enzyme called a prolyl isomerase that is located within the mitochondrial matrix, is an integral part in the formation of the mitochondrial permeability transition pore (mPTP), leading to cell death. Up until now, however, the role of CypD in Alzheimer's disease has not been elucidated.

In this paper, Dr. Yan and colleagues demonstrate that CypD interacts with Aβ peptide within the mitochondria of Alzheimer's disease patients and a transgenic mouse model of Alzheimer's disease. The cortical mitochondria isolated from Alzheimer's disease mice lacking CypD are resistant to Aβ- and Ca2+-induced mitochondria swelling and permeability transition, increase calcium buffering capacity, and attenuate generation of mitochondrial ROS. Furthermore, CypD-deficient neurons protect against Aβ- and oxidative stress-induced cell death. Importantly, deficiency of CycD greatly improved the learning, memory, and synaptic function of an Alzheimer's disease mouse model and alleviated Aβ-mediated reduction of long term potentiation (LTP). Thus, the CypD/Aβ-mediated mitochondrial permeability transition pore directly links to the cellular and synaptic perturbation relevant to the pathogenesis of Alzheimer's disease.


'/>"/>

Contact: Karin Eskenazi
ket2116@columbia.edu
212-305-3900
Columbia University Medical Center
Source:Eurekalert

Related biology news :

1. Scientists show that mitochondrial DNA variants are linked to risk factors for type 2 diabetes
2. Zebrafish to shed light on human mitochondrial diseases
3. New chemical tool kit manipulates mitochondria, reveals insights into drug toxicity
4. Mitochondrial dysfunction and redox signaling in atrial tachyarrhythmia
5. Hebrew University develops novel approach for treating mitochondrial disorders
6. Mitochondrial cholesterol makes response to chemotherapy difficult in hepatic cancer
7. Large reservoir of mitochondrial DNA mutations identified in humans
8. A link between mitochondria and tumor formation in stem cells
9. Newly created cancer stem cells could aid breast cancer research
10. Obesity and lack of exercise could enhance the risk of pancreatic cancer
11. Finding that 1-in-a-billion that could lead to disease
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/2/2016)... June 2, 2016   The Weather Company , an ... Ads, an industry-first capability in which consumers will be able ... to ask questions via voice or text and receive relevant ... Marketers have long sought an advertising solution ... can be personal, relevant and valuable; and can scale across ...
(Date:5/16/2016)...   EyeLock LLC , a market leader of ... an IoT Center of Excellence in Austin, ... of embedded iris biometric applications. EyeLock,s iris ... security with unmatched biometric accuracy, making it the most ... EyeLock,s platform uses video technology to deliver a fast ...
(Date:4/28/2016)... , April 28, 2016 First quarter ... (139.9), up 966% compared with the first quarter of 2015 ... totaled SEK 589.1 M (loss: 18.8) and the operating margin was ... (loss: 0.32) Cash flow from operations was SEK 249.9 ... 2016 revenue guidance is unchanged, SEK 7,000-8,500 M. The ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... June 27, 2016  Liquid Biotech ... funding of a Sponsored Research Agreement with The ... cells (CTCs) from cancer patients.  The funding will ... levels correlate with clinical outcomes in cancer patients ... will then be employed to support the design ...
(Date:6/24/2016)... 24, 2016 Epic Sciences unveiled a ... susceptible to PARP inhibitors by targeting homologous recombination ... The new test has already been incorporated into ... cancer types. Over 230 clinical trials ... pathways, including PARP, ATM, ATR, DNA-PK and WEE-1. ...
(Date:6/23/2016)... WA (PRWEB) , ... June 23, 2016 , ... ... announces the release of its second eBook, “Clinical Trials Patient Recruitment and Retention ... recruitment and retention in this eBook by providing practical tips, tools, and strategies ...
(Date:6/23/2016)... 23, 2016 /PRNewswire/ - FACIT has announced the ... biotechnology company, Propellon Therapeutics Inc. ("Propellon" or ... of a portfolio of first-in-class WDR5 inhibitors for ... as WDR5 represent an exciting class of therapies, ... medicine for cancer patients. Substantial advances have been ...
Breaking Biology Technology: